Enzyme Classification Introductory article

and Nomenclature Article Contents

• Introduction
• General Classification Structure
Andrew G McDonald, Trinity College, Dublin, Ireland
• Notes on Chemical Nomenclature
Sinead Boyce, Trinity College, Dublin, Ireland • Enzyme Classes and Definitions

Keith F Tipton, Trinity College, Dublin, Ireland • Finding Information in ExplorEnz

• Limitations and Problems
Based in part on the previous versions of this eLS article ‘Enzyme • Information and Updates
Classification and Nomenclature’ (2001, 2005).
Online posting date: 15th April 2015

The variety of different names that had been used different enzymes with similar names, or the same enzyme under
for the same enzyme and the fact that some dif- different names.
ferent enzymes were known by the same name In trying to bring some order to the chaotic situation of enzyme
necessitated the development of a rational sys- nomenclature, Dixon and Webb (1958) took a step that was radi-
tem for their classification and nomenclature. cally different from that used in other branches of nomenclature
by classifying enzymes in terms of the reactions they catalysed,
The International Union of Biochemistry devised
rather than by their structures. This system has been adopted
a system of classification that allows the unam-
and developed by the International Union of Biochemistry and
biguous identification of enzymes in terms of the Molecular Biology (IUBMB), through its Joint Commission on
reactions they catalyse. This relies on a numeri- Biochemical Nomenclature in association with the International
cal system (the EC number) to class enzymes in Union of Pure and Applied Chemistry (IUPAC) into the Enzyme
groups according to the types of reaction catalysed Nomenclature list of enzymes classified by the reactions they
and systematic naming that describes the chem- catalyse (the Enzyme List). This has been through several printed
ical reaction involved. This is now in widespread editions, the most recent being published in 1992 (Webb, 1992).
use and the official list of enzymes classified The complete and regularly updated material is now available at
can be found at ExplorEnz – The Enzyme Database the IUBMB Nomenclature Committee’s Enzyme Nomenclature
(http://www.enzyme-database.org). website ExplorEnz (http://www.enzyme-database.org/). These
official data also form the basis of enzyme identification in
many other databases, including the BioCyc Pathway/Genome
Database Collection (2015); Caspi et al. (2014), the BRENDA
Enzyme Information System (2015); Schomburg et al. (2013),
Introduction the Kyoto Encyclopedia of Genes and Genomes (KEGG) (2015);
Kanehisa et al. (2014), the Eawag Biocatalysis/Biodegradation
The need for a rational nomenclature for enzymes can be seen Database (EAWAG-BBD (2015), formerly UM-BBD); Gao
from the plethora of unhelpful names for enzymes in the earlier et al. (2010), the NIST Standard Reference Database on the
literature. Only those who were directly involved might have Thermodynamics of Enzyme-Catalyzed Reactions (2015),
known the difference between the old yellow enzyme and the the SWISSPROT ENZYME (2015) database; Gasteiger et al
new yellow enzyme and what diaphorase, or for that matter (2003) and the Protein Data Bank (PDB) (2015); Berman
DT-diaphorase, catalysed (try EC 1.6.99.1 and EC 1.8.1.4). et al. (2014). The Enzyme List is continuously updated to
Similarly, the reaction catalysed by rhodanese (thiosulfate sul- accommodate new discoveries and new material is avail-
furtransferase: EC 2.8.1.1) was not apparent from its name. An able online as Enzyme Supplements at the ExplorEnz web
enzyme could be known by several different names and the same site. http://www.enzyme-database.org/updates.php. See also:
name was sometimes used for different enzymes and it was not Enzymes: General Properties; Enzymes: The Active Site;
uncommon to find that researchers were reporting studies on Enzyme Activity and Assays; Enzymology Methods; Enzyme
Specificity and Selectivity
Detailed rules for naming and classifying enzymes have been
formulated. Each enzyme is given a unique identifier, the EC
eLS subject area: Biochemistry number, which comprises four components. The first of these
How to cite: represents the type of reaction catalysed, as illustrated in Table 1,
McDonald, Andrew G; Boyce, Sinead; and Tipton, Keith F (April and it is usually a relatively easy matter to assign an enzyme to an
2015) Enzyme Classification and Nomenclature. In: eLS. John overall class. For example, if it oxidises something by reducing
Wiley & Sons, Ltd: Chichester. NAD(P)+ , it is a dehydrogenase classified as EC 1.x.1.–, where
DOI: 10.1002/9780470015902.a0000710.pub3 the number x refers to the group oxidised: 1 for –CHOH–, 2

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 Enzyme Classification and Nomenclature

Table 1 Enzyme classes and the types of reaction they catalysea

Class number Class name Reaction schema
1 Oxidoreductases AH2 + B+ = A + BH + H+ or AH2 + B = A + BH2
2 Transferases AX + B = A + BX
3 Hydrolases A − B + H2 O = AH + BOH
4 Lyases A = B + X − Y = A—B
| |
X Y
5 Isomerases A=B
6 Ligases A + B + NTP = A − B + NDP + P or A + B + NTP = A − B + NMP + PP
a Adapted with permission from McDonald AG & Tipton KF (2014) © John Wiley & Co Ltd.

for aldehyde or ketone, and so on; however, if it transfers a case of dehydrogenases, for example, (NAD+ ) may be used to dis-
phosphate, a diphosphate or another phosphate-containing group tinguish an enzyme that is specific for this acceptor from others
through its phosphate to another substrate, it is a phosphotrans- catalysing a similar transformation but using a different acceptor.
ferase classified as EC 2.7.z.–, where z refers to the nature
of the acceptor group, and so on. The fourth component is a
number that identifies the specific enzyme within that group.
Reaction
Detailed descriptions of the procedures for assigning enzymes The actual reaction catalysed is written, where possible, in the
to specific classes and subclasses and the rules for system- form of a ‘biochemical’ equation 1:
atic enzyme names that have been approved by the IUBMB
Nomenclature Committee have been published in Enzyme
A + B = P + Q (1)
Nomenclature (Webb, 1992) and this is available online at the
ExplorEnz web site http://www.enzyme-database.org/rules.php.
The account here has been adapted from the fuller material This formulation gives no indication of the equilibrium position
in that source, which should be consulted if further detail is of the reaction or the net direction of flux through the enzyme in
required. vivo. Indeed, in some cases, an enzymatic reaction can proceed
in a thermodynamically unfavoured direction in a metabolic path-
way because of the effective removal of one of the reactants in a
General Classification Structure subsequent reaction. The direction chosen for the reaction is, by
convention, the same for all the enzymes in a given class, even
The basic layout of the classification entry for each enzyme is if this direction has not been demonstrated for all. Frequently,
described here with some indication of the guidelines followed. such biochemical equations are neither fully charge-balanced nor
Further details of the principles governing the nomenclature of mass-balanced.
individual enzyme classes are given in the following sections.

EC number Notes on Chemical Nomenclature

The classification number, which is made up of four numbers
separated by periods, identifies the enzyme by the reaction catal- Although a detailed description of chemical nomenclature is
ysed. It is intended to provide an unambiguous identifier for that beyond the scope of this article, some comments are necessary
enzyme and is also valuable for relating the information to other because the fearsome names used are often difficult for a bio-
databases. chemist to understand. The aim of the chemist is to be able to
name a compound in such a way that anyone who knows the
rules of chemical nomenclature can write down its chemical
Accepted name
structure and formula from that name. Therefore, it must be
The most commonly used name for the enzyme is usually used, unambiguous in terms of all the chemical groups that make up
provided that it is neither ambiguous nor misleading. A num- the compound, how and where they are linked together, and
ber of generic words indicating reaction types may be used in the compound’s stereochemistry. This does lead to names that
Accepted names: for example, dehydrogenase, reductase, oxi- are not much help for general use; for example, the neurotrans-
dase, peroxidase, kinase, tautomerase, deaminase, dehydratase. mitter noradrenaline (norepinephrine) has a systematic name
Where additional information is needed to make the reaction (R)-4-(2-amino-1-hydroxyethyl)-1,2-benzenediol; the antibi-
clear, a word or phrase indicating the reaction or a product may otic benzylpenicillin is [2S-(2α,5α,6β)]-3,3-dimethyl-7-oxo-6-
be added in parentheses after the second part of the name, for [(phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carb-
example, (ADP-forming), (dimerising), (CoA-acylating). In the oxylic acid; and aspirin is 2-(acetyloxy)benzoic acid.

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 Enzyme Classification and Nomenclature

The basic rules for writing down the systematic name of a com- catalyses reaction 2.
pound are, first, to take a basic (or root) structure or its derivative.
For example, benzoic acid is the derivative of the root benzene ATP + D-fructose 6-phosphate
in the case of aspirin. The substituents are then written before
= ADP + D-fructose 1, 6-bisphosphate (2)
it, with the position of each substituent and any stereochemistry
being identified. There are several possible modifications of this
Note that the term bisphosphate is used here rather than diphos-
procedure and it is possible to write more than one systematic
phate. In order to avoid confusion, diphosphate is used only for
name that is more-or-less unambiguous (see, e.g. the alternative
cases where the two phosphates are linked together (as in adeno-
names that have been used for noradrenaline in ChemSpider).
sine diphosphate; ADP), whereas bisphosphates have the two
Variations arise, for example, from the choice of root compound
phosphates attached to separate groups in the molecule.
and the order in which the substituents are written. Where sys-
When a substrate name has two words, there is a potential
tematic names are used for compounds, the enzyme classification
problem using them in enzyme names. Glucose-6-phosphate
system uses the IUPAC system, which uses rather few root com-
1-dehydrogenase (EC 1.1.1.49) catalyses reaction 3.
pounds and writes the substituents in alphabetical order (e.g.
amino before hydroxy before methyl, and so on). The summary
D-glucose 6-phosphate + NADP+ = 6-phospho-D
given glosses over many of the complexities of systematic chem-
ical nomenclature, and fuller details of the complexities of sys- -glucono-1, 5-lactone + NADPH + H+ (3)
tematic chemical nomenclature and fuller details of the rules and
their application can be found in Favre and Powell (2013) with an But in order to indicate that the substrate oxidised is glucose
older version available online at IUPAC Nomenclature of Organic 6-phosphate, not just phosphate, an extra hyphen is added to the
Compounds (1993). A full list of IUPAC and IUBMB recommen- substrate name in forming the enzyme name.
dations on chemical and biochemical nomenclature can be found In denoting stereochemistry, the IUPAC rules prefer the R- and
at the IUPAC & IUBMB (2013) Nomenclature recommendations S- system and this is generally used in enzyme nomenclature.
web site. However, in the case of sugars and amino acids and sugars, the
Chemists use fewer root structures than biochemists. For D- and L- designations are so well known that they are followed

example, biochemists know the amino acid tryptophan and in the enzyme list. The use of italics in chemical names can at
that it can be decarboxylated to tryptamine. They there- first seem rather odd, but the simplest way of thinking about it
fore have no trouble with naming the hormone melatonin as is to consider how one would look up the name of a compound
N-acetyl-5-methoxytryptamine. However, if a chemist does in an index, for example, N-acetyl-5-methoxytryptamine would
not accept tryptamine as a root structure, the name becomes be found by searching through A for acetyl not N for N-acetyl.
N-[2-(5-methoxy-1H-indol-3-yl)ethyl]acetamide. Because the Clearly, the same applies to R- and S-isomers. Therefore, the
enzyme classification system is primarily designed for bio- italic can be taken to mean ‘do not bother to look under this
chemists, the biochemical names are frequently used, where letter in any index’. Having adopted this way of doing things,
these are widely known. However, collaboration with IUPAC it is logical also to use italics for these when they occur in the
ensures that the systematic names can be readily found from middle of a name. The exceptions to this general rule are the D-
these in their literature and a Glossary is provided for each entry, and L- designations, which are not italicised, but are written, by
where appropriate, to give the IUPAC or alternative names for convention, in a smaller size than normal.
the compounds referred to. The Glossary can also be accessed
separately, at http://www.enzyme-database.org/glossary.php,
where the entries are linked to the ChemSpider database (2015);
Enzyme Classes and Definitions
Williams and Tkachenko (2014), to allow their structures to be
In the examples given here, the Glossary entries, links to other
viewed. The biochemical literature contains many abbreviated
databases and references have been omitted to save space.
or contracted names, such as AdoMet, ATP and GlcNAc, which
are frequently used without definition. In order to help those
working in other fields, a list of these and their definitions is
Class 1. Oxidoreductases
provided at http://www.enzyme-database.org/abbrev.php. This class contains the enzymes catalysing oxidation reactions.
It should be noted that the systematic names of noradrenaline Because the oxidation of one group must be accompanied by the
and melatonin are single ‘words’, which can contain lots of reduction of another, they are grouped together as oxidoreduc-
hyphens in them, and generally systematic names are written as tases. The Systematic enzyme name is in the form donor:acceptor
single ‘words’. Among the few exceptions to this general rule oxidoreductase. The substrate that is being oxidised is regarded
are acids, including phosphates, as shown by the examples of as being the donor. The Accepted name is frequently of the form
penicillin and aspirin, where ‘acid’ is written as a separate word. donor dehydrogenase. Although the term reductase is sometimes
This also applies to biochemical names, where, for example, used as an alternative where the reaction is known to proceed
creatine phosphate is written as two words, although it is possible in that direction, it is important to remember that the Accepted
to write the compound as a single word by rearranging the name name does not necessarily define direction in which the reaction
to phosphocreatine. An example of such rearrangement is the is believed to proceed. The term donor oxidase is used only when
name 6-phosphofructokinase for the enzyme (EC 2.7.1.11) that O2 is the acceptor.

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 Enzyme Classification and Nomenclature

The second figure in the EC number of the oxidoreductases The Systematic name is in the form donor:acceptor group-
denotes the type of group in the hydrogen-donor substrate that transferase. The Accepted names are normally formed according
is oxidised or reduced. The third number denotes the hydro- to acceptor grouptransferase or donor grouptransferase.
gen acceptor: 1 denotes NAD(P)+ , 2 a cytochrome, 3 molecular Sometimes transferase reactions can be considered in different
oxygen, 4 a disulfide, 5 a quinone or similar compound, 6 a ways; for example, the general reaction shown may be regarded
nitrogenous group, 7 an iron–sulfur protein, and 8 a flavin. The as a transfer of the group Y from X to Z, and would therefore be
number 98 is used for other known acceptors and 99 is for cases termed a Y-transferase. However, it could also be considered as a
where the physiological acceptor is, as yet, unknown. This last breaking of the X–Y bond by the introduction of Z. For example,
group contains a number of enzymes that have been shown to where Z represents phosphate, the process is often referred to
work with synthetic acceptors, such as 2,6-dichloroindophenol as phosphorolysis and the enzyme catalysing the reaction as
or phenazine methosulfate, but where the physiological accep- a phosphorylase. Although that may be used in the Accepted
tor is unknown. It is intended that these should be transferred to name, these enzymes are classified as phosphotransferases, for
more descriptive sub-subclasses when the natural acceptor has systematic purposes.
been identified. The aminotransferase (transaminase) reactions involve the
For subclasses 1.13 and 1.14, a different classification scheme transfer of an –NH2 group and H to a compound containing a
is used, as these enzymes catalyse the incorporation of oxygen carbonyl group, in exchange for the =O of that group (reaction 5).
into the substrate. The Accepted names are generally monooxy-
genase or dioxygenase, depending on whether one or two atoms R1 –CHNH2 –R2 + R3 –CO–R4 = R1 –CO–R2
of oxygen are incorporated into the substance oxidised.
Table 2 summarises the structure of Class 1. + R3 –CHNH2 –R4 (5)

Examples Thus, the reaction could be regarded as being an oxidative

deamination of the donor (e.g. an amino acid) linked to the
reductive amination of the acceptor (e.g. oxo acid). Therefore,
these enzymes might be classified as oxidoreductases. However,
EC 1.1.1.14
because the unique distinctive feature of the reaction is the trans-
Accepted name: L-iditol 2-dehydrogenase
+
fer of the amino group, these enzymes are classified as amino-
Reaction: L-iditol + NAD = L-sorbose + NADH
+
transferases (sub-subclass 2.6.1).
+H
The second figure in the code number of the transferases
Other name(s): polyol dehydrogenase; sorbitol
denotes the general nature of the group transferred (2.1 for a
dehydrogenase
+
one-carbon group; 2.2 for an aldehydic or ketonic group; 2.3
Systematic name: L-iditol:NAD 2-oxidoreductase
for an acyl group, etc.) and the third number further speci-
Comments: Also acts on D-glucitol (giving
fies that group (2.1.1 methyltransferase; 2.1.2; formyltransferase,
D-fructose) and other closely related
etc.). The exception is the case of the enzymes transferring
sugar alcohols.
phosphorus-containing groups (subclass 2.7), where the third
EC 1.14.13.59
6
number specifies the nature of the acceptor group.
Accepted name: L-lysine N -monooxygenase (NADPH)
+ 6
Table 3 summarises the structure of Class 2.
Reaction L-lysine + NADPH + H + O2 = N -
hydroxy-L-lysine + NADP+ + H2 O Example
Other name(s): lysine N6 -hydroxylase; L-lysine
6-monooxygenase (NADPH)
(ambiguous) EC 2.1.1.114
Systematic name: L-lysine, NADPH:oxygen
Accepted name: polyprenyldihydroxybenzoate
oxidoreductase (6-hydroxylating) methyltransferase
Comments: A flavoprotein (FAD). The enzyme xReaction: S-adenosyl-L-methionine + 3,4-dihydroxy-
from strain EN 222 of Escherichia 5-all-trans-polyprenylbenzoate = S-
coli is highly specific for L-lysine; adenosyl-L-homocysteine + 3-methoxy-
L-ornithine and L-homolysine are, for
4-hydroxy-5-all-trans-
example, not substrates polyprenylbenzoate
Other name(s): 3,4-dihydroxy-5-hexaprenylbenzoate
methyltrans-
ferase;dihydroxyhexaprenylbenzoate
methyltransferase; COQ3 (gene name);
Class 2. Transferases Coq3 O-methyltransferase; DHHB
O-methyltransferase
These enzymes transfer a group from one substrate (the donor) to Systematic name: S-adenosyl-L-methionine:3,4-dihydroxy-
another (the acceptor) according to the general reaction 4: 5-all-trans-polyprenylbenzoate
3-O-methyltransferase
X–Y + Z = X + Y–Z (4)

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 Enzyme Classification and Nomenclature

Comments: This enzyme is involved in ubiquinone EC 1.3.1 With NAD+ or NADP+ as acceptor
biosynthesis. Ubiquinones from different EC 1.3.2 With a cytochrome as acceptor
organisms have a different number of EC 1.3.3 With oxygen as acceptor
prenyl units (e.g.,ubiquinone-6 in EC 1.3.4 With a disulfide as acceptor
Saccharomyces, ubiquinone-9 in rat and EC 1.3.5 With a quinone or related compound as acceptor
ubiquinone-10 in human), and thus the EC 1.3.7 With an iron-sulfur protein as acceptor
natural substrate for the enzymes from EC 1.3.8 With a flavin as acceptor
different organisms has a different EC 1.3.98 With other, known, acceptors
number of prenyl units. However, the EC 1.3.99 With other, unknown, acceptors
enzyme usually shows a low degree of EC 1.4 Acting on the CH-NH2 group of donors
specificity regarding the number of EC 1.4.1 With NAD+ or NADP+ as acceptor
prenyl units. For example, the human EC 1.4.2 With a cytochrome as acceptor
COQ3 enzyme can restore biosynthesis EC 1.4.3 With oxygen as acceptor
of ubiquinone-6 in coq3 deletion EC 1.4.4 With a disulfide as acceptor
mutants of yeast [3]. The enzymes from EC 1.4.5 With a quinone or other compound as acceptor
yeast and rat also catalyse the EC 1.4.7 With an iron-sulfur protein as acceptor
methylation of 3-demethylubiquinol-6 EC 1.4.9 With a copper protein as acceptor
and 3-demethylubiquinol-9, respectively EC 1.4.99 With other, unknown, acceptors
[2] (this activity is classified as EC EC 1.5 Acting on the CH-NH group of donors
2.1.1.64, 3-demethylubiquinol EC 1.5.1 With NAD+ or NADP+ as acceptor
3-O-methyltransferase) EC 1.5.3 With oxygen as acceptor
EC 1.5.4 With a disulfide as acceptor
EC 1.5.5 With a quinone or similar compound as acceptor
Class 3. Hydrolases EC 1.5.7 With an iron-sulfur protein as acceptor
EC 1.5.8 With a flavin or flavoprotein as acceptor
These enzymes catalyse the hydrolytic cleavage of bonds such EC 1.5.99 With other, unknown, acceptors
as C–O, C–N, C–C and some other bonds, including phosphoric EC 1.6 Acting on NADH or NADPH
anhydride bonds. The overlapping specificities of many of these EC 1.6.1 With NAD+ or NADP+ as acceptor
enzymes make it difficult to formulate general rules that are EC 1.6.2 With a heme protein as acceptor
applicable to all members of this class. The Systematic name EC 1.6.3 With oxygen as acceptor
usually takes the form substrate X-hydrolase, where X is the EC 1.6.4 With a disulfide as acceptor (deleted sub-
group removed by hydrolysis. The Accepted name is, in many subclass)
cases, formed by the name of the substrate with the suffix -ase. EC 1.6.5 With a quinone or similar compound as acceptor
It is understood that the name of the substrate with this suffix EC 1.6.6 With a nitrogenous group as acceptor
indicates a hydrolytic enzyme. EC 1.6.7 With an iron-sulfur protein as acceptor (deleted
sub-subclass)
Table 2 Class 1. Oxidoreductases (partial list) EC 1.6.8 With a flavin as acceptor (deleted sub-subclass)
EC 1.6.99 With other, unknown, acceptors
EC 1 Oxidoreductases EC 1.7 Acting on other nitrogenous compounds as donors
EC 1.1 Acting on the CH-OH group of donors EC 1.7.1 With NAD+ or NADP+ as acceptor
EC 1.1.1 With NAD+ or NADP+ as acceptor EC 1.7.2 With a cytochrome as acceptor
EC 1.1.2 With a cytochrome as acceptor EC 1.7.3 With oxygen as acceptor
EC 1.1.3 With oxygen as acceptor EC 1.7.5 With a quinone or similar compound as acceptor
EC 1.1.4 With a disulfide as acceptor EC 1.7.6 With a nitrogenous group as acceptor
EC 1.1.5 With a quinone or similar compound as acceptor EC 1.7.7 With an iron-sulfur protein as acceptor
EC 1.1.9 With a copper protein as acceptor EC 1.7.9 With a copper protein as acceptor
EC 1.1.98 With other, known, acceptors EC 1.7.99 With other, unkown, acceptors
EC 1.1.99 With other, unknown, acceptors EC 1.8 Acting on a sulfur group of donors
EC 1.2 Acting on the aldehyde or oxo group of donors EC 1.8.1 With NAD+ or NADP+ as acceptor
EC 1.2.1 With NAD+ or NADP+ as acceptor EC 1.8.2 With a cytochrome as acceptor
EC 1.2.2 With a cytochrome as acceptor EC 1.8.3 With oxygen as acceptor
EC 1.2.3 With oxygen as acceptor EC 1.8.4 With a disulfide as acceptor
EC 1.2.4 With a disulfide as acceptor EC 1.8.5 With a quinone or similar compound as acceptor
EC 1.2.5 With a quinone or similar compound as acceptor EC 1.8.6 With a nitrogenous group as acceptor (deleted
EC 1.2.7 With an iron-sulfur protein as acceptor sub-subclass)
EC 1.2.99 With other, unknown, acceptors EC 1.8.7 With an iron-sulfur protein as acceptor
EC 1.3 Acting on the CH-CH group of donors EC 1.8.98 With other, known, acceptors

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 Enzyme Classification and Nomenclature

Table 3 Class 2. Transferases

EC 2.8 Transferring sulfur-containing groups
EC 2 Transferases EC 2.8.1 Sulfurtransferases
EC 2.1 Transferring one-carbon groups EC 2.8.2 Sulfotransferases
EC 2.1.1 Methyltransferases EC 2.8.3 CoA-transferases
EC 2.1.2 Hydroxymethyl-, formyl- and related EC 2.8.4 Transferring alkylthio groups
transferases EC 2.9 Transferring selenium-containing groups
EC 2.1.3 Carboxy- and carbamoyltransferases EC 2.9.1 Selenotransferases
EC 2.1.4 Amidinotransferases EC 2.10 Transferring molybdenum- or tungsten-containing
EC 2.2 Transferring aldehyde or ketonic groups groups
EC 2.2.1 Transketolases and transaldolases EC 2.10.1 Molybdenumtransferases or tungstentransferases
EC 2.3 Acyltransferases with sulfide groups as acceptors
EC 2.3.1 Transferring groups other than aminoacyl groups
EC 2.3.2 Aminoacyltransferases
EC 2.3.3 Acyl groups converted into alkyl groups on
transfer
EC 2.4 Glycosyltransferases Hydrolytic enzymes might be classified as transferases,
EC 2.4.1 Hexosyltransferases because hydrolysis itself can be regarded as transfer of a specific
EC 2.4.2 Pentosyltransferases group to water as the acceptor. Yet, in most cases, the reaction
EC 2.4.99 Transferring other glycosyl groups with water as the acceptor was discovered earlier and is con-
EC 2.5 Transferring alkyl or aryl groups, other than sidered as the main physiological function of the enzyme. This
methyl groups is why such enzymes are classified as hydrolases rather than as
EC 2.5.1 Transferring alkyl or aryl groups, other than transferases.
methyl groups (only sub-subclass identified to The second number indicates the nature of the bond hydrol-
date) ysed, and the third normally specifies the nature of the
substrate, for example, in the esterases the carboxylic ester
EC 2.6 Transferring nitrogenous groups
hydrolases (3.1.1), thiolester hydrolases (3.1.2), phosphoric
EC 2.6.1 Transaminases
monoester hydrolases (3.1.3); in the glycosidases, the glycosi-
EC 2.6.2 Amidinotransferases (deleted sub-subclass) dases hydrolysing O- and S-glycosyl compounds (3.2.1) and
EC 2.6.3 Oximinotransferases N-glycosidases (3.2.2).
EC 2.6.99 Transferring other nitrogenous groups The peptidases (also termed proteases, proteinases , proteolytic
EC 2.7 Transferring phosphorus-containing groups enzymes or peptide hydrolases) in subclass 3.4. cannot be accom-
EC 2.7.1 Phosphotransferases with an alcohol group as modated within the general scheme used for other enzymes. It
acceptor is not even possible to give them meaningful EC numbers or
EC 2.7.2 Phosphotransferases with a carboxy group as unambiguous Systematic names because of variable specificities
acceptor and great similarities between the actions of different peptidases.
EC 2.7.3 Phosphotransferases with a nitrogenous group as These enzymes were grouped into two sets of sub-subclasses, the
acceptor endopeptidases (3.4.21 to 3.4.25 and 3.4.99) and exopeptidases
EC 2.7.4 Phosphotransferases with a phosphate group as (3.4.11 to 3.4.19), with the third number also depending on the
acceptor catalytic mechanism. However, this proved inadequate because
EC 2.7.5 Phosphotransferases with regeneration of of the large number of peptidases catalysing similar reactions
donors, apparently catalysing intramolecular and it was decided to cease adding new peptidases to the list but
transfers (deleted sub-subclass) to rely on the specific MEROPS (2014) database which uses an
entirely different classification system for these enzymes (Rawl-
EC 2.7.6 Diphosphotransferases
ings et al., 2014). Entries for peptidases that were already in the
EC 2.7.7 Nucleotidyltransferases
Enzyme List have been retained, with links to MEROPS. See
EC 2.7.8 Transferases for other substituted phosphate also: Proteases
groups Table 4 summarises the structure of Class 3.
EC 2.7.9 Phosphotransferases with paired acceptors
EC 2.7.10 Protein-tyrosine kinases Examples
EC 2.7.11 Protein-serine/threonine kinases
EC 2.7.12 Dual-specificity kinases (those acting on Ser/Thr
and Tyr residues) EC 3.1.1.3
EC 2.7.13 Protein-histidine kinases Accepted name: triacylglycerol lipase
EC 2.7.14 Protein-arginine kinases Reaction: triacylglycerol + H2 O = diacylglycerol + a
EC 2.7.99 Other protein kinases carboxylate

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 Enzyme Classification and Nomenclature

Other name(s): lipase (ambiguous); butyrinase;

tributyrinase; Tween hydrolase; steapsin; EC 3.1.11 Exodeoxyribonucleases producing
triacetinase; tributyrin esterase; 5′ -phosphomonoesters
Tweenase; amno N-AP; Takedo EC 3.1.12 Exodeoxyribonucleases producing
1969-4-9; Meito MY 30; Tweenesterase; 3′ -phosphomonoesters
GA 56; capalase L; triglyceride EC 3.1.13 Exoribonucleases producing
hydrolase; triolein hydrolase; 5′ -phosphomonoesters
tween-hydrolyzing esterase; amano CE; EC 3.1.14 Exoribonucleases producing
cacordase; triglyceridase; triacylglycerol 3’-phosphomonoesters
ester hydrolase; amano P; amano AP; EC 3.1.15 Exonucleases that are active with either ribo- or
PPL; glycerol-ester hydrolase; GEH; deoxyribonucleic acids and produce
meito Sangyo OF lipase; hepatic lipase; 5′ -phosphomonoesters
lipazin; post-heparin plasma EC 3.1.16 Exonucleases that are active with either ribo- or
protamine-resistant lipase; salt-resistant deoxyribonucleic acids and produce
post-heparin lipase; heparin releasable 3′ -phosphomonoesters
hepatic lipase; amano CES; amano B; EC 3.1.21 Endodeoxyribonucleases producing
tributyrase; triglyceride lipase; liver 5′ -phosphomonoesters
lipase; hepatic monoacylglycerol EC 3.1.22 Endodeoxyribonucleases producing
acyltransferase 3′ -phosphomonoesters
Systematic name: triacylglycerol acylhydrolase EC 3.1.23 Site-specific endodeoxyribonucleases: cleavage
Comments: The pancreatic enzyme acts only on an is sequence specific (deleted sub-subclass)
ester–water interface; the outer ester EC 3.1.24 Site specific endodeoxyribonucleases: cleavage
links are preferentially hydrolysed is not sequence specific (deleted sub-subclass)
EC 3.1.2.23 EC 3.1.25 Site-specific endodeoxyribonucleases that are
Accepted name: 4-hydroxybenzoyl-CoA thioesterase specific for altered bases
Reaction: 4-hydroxybenzoyl-CoA + H2 O = 4- EC 3.1.26 Endoribonucleases producing
hydroxybenzoate + CoA 5′ -phosphomonoesters
Systematic name: 4-hydroxybenzoyl-CoA hydrolase EC 3.1.27 Endoribonucleases producing
Comments: This enzyme is part of the bacterial 3′ -phosphomonoesters
2,4-dichlorobenzoate degradation EC 3.1.30 Endoribonucleases that are active with either
pathway ribo- or deoxyribonucleic acids and produce
5′ -phosphomonoesters
EC 3.1.31 Endoribonucleases that are active with either
ribo- or deoxyribonucleic acids and produce
Class 4. Lyases 3′ -phosphomonoesters
EC 3.2 Glycosylases
These enzymes cleave C–C, C–O, C–N and other bonds by EC 3.2.1 Glycosidases, i.e. enzymes that hydrolyse O-
means other than hydrolysis or oxidation. They differ from other and S-glycosyl compounds
enzymes in that two substrates may be involved in one reaction EC 3.2.2 Hydrolysing N-glycosyl compounds
direction but only one in the other. When they act on the single EC 3.2.3 Hydrolysing S-glycosyl compounds (deleted
substrate, the reaction can be regarded as an internal transfer in sub-subclass)
which a molecule is eliminated, leaving double bonds or rings. EC 3.3 Acting on ether bonds
The Systematic name is formed according to the pattern sub- EC 3.3.1 Thioether and trialkylsulfonium hydrolases
strate group-lyase. The hyphen is an important part of the name EC 3.3.2 Ether hydrolases
EC 3.4 Acting on peptide bonds (peptidases)
EC 3.4.1 α-Amino-acyl-peptide hydrolases (deleted
Table 4 EC 3. Hydrolases (partial list) sub-subclass)
EC 3 Hydrolases EC 3.4.2 Peptidyl-amino-acid hydrolases (deleted
EC 3.1 Acting on ester bonds sub-subclass)
EC 3.1.1 Carboxylic-ester hydrolases EC 3.4.3 Dipeptide hydrolases (deleted sub-subclass)
EC 3.1.2 Thioester hydrolases EC 3.4.4 Peptidyl peptide hydrolases (deleted sub-
EC 3.1.3 Phosphoric-monoester hydrolases subclass)
EC 3.1.4 Phosphoric-diester hydrolases EC 3.4.11 Aminopeptidases
EC 3.1.5 Triphosphoric-monoester hydrolases EC 3.4.12 Peptidylamino-acid hydrolases or acylamino-
EC 3.1.6 Sulfuric-ester hydrolases acid hydrolases (deleted sub-subclass)
EC 3.1.7 Diphosphoric-monoester hydrolases EC 3.4.13 Dipeptidases
EC 3.1.8 Phosphoric-triester hydrolases EC 3.4.14 Dipeptidyl-peptidases and tripeptidyl-peptidases
(continued overleaf )

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 Enzyme Classification and Nomenclature

Table 4 (Continued) The second number indicates the bond broken: 4.1 enzymes are
EC 3.4.15Peptidyl-dipeptidases carbon–carbon lyases, 4.2 enzymes are carbon–oxygen lyases,
EC 3.4.16Serine-type carboxypeptidases and so on. The third number 4 gives further information on the
EC 3.4.17Metallocarboxypeptidases group eliminated (e.g. CO2 in 4.1.1 and H2 O in 4.2.1).
EC 3.4.18Cysteine-type carboxypeptidases Table 5 summarises the structure of Class 4.
EC 3.4.19Omega peptidases Example
EC 3.4.21Serine endopeptidases
EC 3.4.22Cysteine endopeptidases
EC 3.4.23Aspartic endopeptidases EC 4.1.2.46
EC 3.4.24Metalloendopeptidases Accepted name: aliphatic (R)-hydroxynitrile lyase
EC 3.4.25Threonine endopeptidases Reaction: (2R)-2-hydroxy-2-methylbutanenitrile =
EC 3.4.99Endopeptidases of unknown catalytic cyanide + butan-2-one
mechanism (sub-subclass is currently empty) Other name(s): (R)-HNL; (R)-oxynitrilase;
EC 3.5 Acting on carbon–nitrogen bonds, other than (R)-hydroxynitrile lyase; LuHNL
peptide bonds Systematic name: (2R)-2-hydroxy-2-methylbutanenitrile
EC 3.5.1 In linear amides butan-2-one-lyase (cyanide forming)
EC 3.5.2 In cyclic amides Comments: The enzyme contains Zn2+ [1]. The
EC 3.5.3 In linear amidines enzyme catalyses the stereoselective
EC 3.5.4 In cyclic amidines synthesis of aliphatic (R)-cyanohydrins
EC 3.5.5 In nitriles [1]. No activity towards mandelonitrile
EC 3.5.99 In other compounds and 4-hydroxymandelonitrile [5].
EC 3.6 Acting on acid anhydrides Natural substrates for the
EC 3.6.1 In phosphorus-containing anhydrides (R)-oxynitrilase from Linum
EC 3.6.2 In sulfonyl-containing anhydrides usitatissimum are acetone and
EC 3.6.3 Acting on acid anhydrides to catalyse butan-2-one, which are the building
transmembrane movement of substances blocks of the cyanogen glycosides in
EC 3.6.4 Acting on acid anhydrides to facilitate cellular Linum, linamarin and lotaustralin, or
and subcellular movement linustatin and neolinustatin,
EC 3.6.5 Acting on GTP to facilitate cellular and respectively [4]
subcellular movement
EC 3.7 Acting on carbon–carbon bonds
EC 3.7.1 In ketonic substances

Class 5. Isomerases
which, to avoid confusion, should not be omitted, for example, These enzymes catalyse geometric or structural changes within
hydro-lyase not ‘hydrolyase’. In the Accepted names, expres- one molecule. According to the type of isomerism involved, they
sions such as decarboxylase or aldolase (in case of elimination may be called racemases, epimerases, cis–trans-isomerases, iso-
of CO2 or aldehyde, respectively) are used. Dehydratase is used merases, tautomerases, mutases or cycloisomerases. The second
for those enzymes catalysing the elimination of water. In cases number denotes the type of isomerism involved, and the third
where the reverse reaction is much more important, or the only number the type of substrate. In some cases, the reaction involves
one demonstrated, synthase (not synthetase) may be used in the an intermolecular oxidoreduction, but because the donor and
name. Although the term SYNTHETASE has sometimes been used in acceptor groups are in the same molecule they are classified as
the names of enzymes from this class, the usage is discouraged isomerases rather than as oxidoreductases, even though they may
in order to prevent confusion with enzymes from Class 6 (see contain firmly bound NAD+ or NADP+ .
subsequent text). Table 6 summarises the structure of Class 5.
Various subclasses of the lyases include pyridoxal-phosphate
enzymes that catalyse the elimination of a β- or γ-substituent from Example
an α-amino acid, followed by a replacement of this substituent by
some other group. In the overall replacement reaction, no unsat-
urated end product is formed; therefore, these enzymes might
formally be classified as alkyltransferases (EC 2.5.1.–). How- EC 5.1.99.4
ever, there is ample evidence that the replacement is a two-step Accepted name: α-methylacyl-
reaction involving the transient formation of enzyme-bound α,β- CoA racemase
(or β,γ-)unsaturated amino acids. According to the rule that Reaction: (2S)-2-methylacyl-CoA = (2R)-2-
the first reaction is indicative for classification, these enzymes methylacyl-CoA
are correctly classified as lyases. Examples are tryptophan syn- Systematic name: 2-methylacyl-CoA 2-epimerase
thase (EC 4.2.1.20) and cystathionine β-synthase (EC 4.2.1.22).

8 eLS © 2015, John Wiley & Sons, Ltd. www.els.net

 Enzyme Classification and Nomenclature

Comments: α-methyl-branched acyl-CoA derivatives The second number indicates the bond formed: 6.1 for C–O
with chain lengths of more than C10 are bonds (e.g., enzymes acylating tRNA), 6.2 for C–S bonds
substrates. Also active towards some (acyl-CoA derivatives), etc. Sub-subclasses are only in use in the
aromatic compounds (e.g. ibuprofen) C–N ligases (6.3), which include the amide synthases (6.3.1), the
and bile acid intermediates, such as peptide synthases (6.3.2), enzymes forming heterocyclic rings
trihydroxycoprostanoyl-CoA. Not active (6.3.3), and so on.
towards free acids Table 7 summarises the structure of Class 6.
Example

Table 5 Class 4. Lyases

EC 6.2.1.1
EC 4 Lyases Accepted name: acetate-CoA ligase
EC 4.1 Carbon–carbon lyases Reaction: ATP + acetate + CoA = AMP
EC 4.1.1 Carboxy-lyases + diphosphate + acetyl-CoA
EC 4.1.2 Aldehyde-lyases
EC 4.1.3 Oxo-acid-lyases
EC 4.1.99 Other carbon–carbon lyases Other name(s): acetyl-CoA synthetase; acetyl activating
EC 4.2 Carbon–oxygen lyases enzyme; acetate thiokinase;
EC 4.2.1 Hydro-lyases acyl-activating enzyme; acetyl
EC 4.2.2 Acting on polysaccharides coenzyme A synthetase; acetic
EC 4.2.3 Acting on phosphates thiokinase; acetyl CoA ligase; acetyl
EC 4.2.99 Other carbon–oxygen lyases CoA synthase; acetyl-coenzyme A
EC 4.3 Carbon–nitrogen lyases synthase; short chain fatty acyl-CoA
EC 4.3.1 Ammonia-lyases synthetase; short-chain acyl-coenzyme
EC 4.3.2 Amidine-lyases A synthetase; ACS
EC 4.3.3 Amine-lyases Systematic name: acetate:CoA ligase (AMP-forming)
EC 4.3.99 Other carbon–nitrogen lyases Comments: Also acts on propanoate and propenoate
EC 4.4 Carbon–sulfur lyases
EC 4.4.1 Carbon–sulfur lyases (only sub-subclass
identified to date)
EC 4.5 Carbon–halide lyases
EC 4.5.1 Carbon–halide lyases (only sub-subclass Finding Information in ExplorEnz
identified to date)
EC 4.6 Phosphorus–oxygen lyases ExplorEnz is a relational database of the IUBMB Enzyme List.
EC 4.6.1 Phosphorus–oxygen lyases (only sub-subclass One can search by EC number, name substrate or any other
identified to date) selected word in each or all of the entry fields. Substring searching
EC 4.7 carbon–phosphorus lyases of each of its fields, along with full-text searching and Boolean
EC 4.7.1 carbon–phosphorus lyases (only sub-subclass (AND, OR, NOT) filtering is also facilitated. Search results can
identified to date) be tailored to display only fields selected by the user, in formats
EC 4.99 Other lyases suitable for screen or printing. Downloads of the database are
EC 4.99.1 Sole sub-subclass for lyases that do not belong provided as SQL or XML. The Quick-Start Guide, found under
in the other subclasses the information tab on the ExplorEnz home page contains a
description of the searching and download options. The complete
Abbreviations list and Glossary can also be found under this
Class 6. Ligases tab, along with the classification rules and an FAQ (frequently
asked questions) list on enzyme classification and how to use the
These enzymes catalyse the joining together (ligating) of two database.
molecules with the concomitant hydrolysis of a diphosphate
bond in ATP or a similar triphosphate. The Systematic enzyme
name takes the form A:B ligase, with a qualifier, if necessary Limitations and Problems
in parentheses to indicate the nucleoside triphosphate involved.
Because ATP, for example, may be converted to ADP or AMP Isoenzymes may not be easily accommodated in any system of
in the reaction, it is the product that is specified, for example, classification simply in terms of reaction catalysed. For example,
(ADP-forming) or (AMP-forming). The Accepted name often there are about 20 different isoenzymes of alcohol dehydrogenase
takes the form A–B ligase or A–B synthase, which emphasises in human liver. These have been organised into broad groups in
the synthetic nature of the reaction. The name synthetase is no terms of their electrophoretic mobilities and, more precisely, in
longer used, but may be found under other names. terms of their sequences and genetic origin. Members of these

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 Enzyme Classification and Nomenclature

Table 6 Class 5. Isomerases Table 7 Class 6. Lyases

EC 5 Isomerases EC 6 Ligases
EC 5.1 Racemases and epimerases EC 6.1 Forming carbon–oxygen bonds
EC 5.1.1 Acting on amino acids and derivatives EC 6.1.1 Ligases forming aminoacyl-tRNA and related
EC 5.1.2 Acting on hydroxy acids and derivatives compounds
EC 5.1.3 Acting on carbohydrates and derivatives EC 6.1.2 Acid–alcohol ligases (ester synthases)
EC 5.1.99 Acting on other compounds EC 6.2 Forming carbon–sulfur bonds
EC 5.2 cis–trans-Isomerases EC 6.2.1 Acid–thiol ligases
EC 5.2.1 cis–trans-Isomerases (only sub-subclass EC 6.3 Forming carbon–nitrogen bonds
identified to date) EC 6.3.1 Acid–ammonia (or amine) ligases (amide
EC 5.3 Intramolecular oxidoreductases synthases)
EC 5.3.1 Interconverting aldoses and ketoses, and related EC 6.3.2 Acid–amino-acid ligases (peptide synthases)
compounds EC 6.3.3 Cyclo-ligases
EC 5.3.2 Interconverting keto- and enol-groups EC 6.3.4 Other carbon–nitrogen ligases
EC 5.3.3 Transposing C=C bonds EC 6.3.5 Carbon–nitrogen ligases with glutamine as
EC 5.3.4 Transposing S–S bonds amido-N-donor
EC 5.3.99 Other intramolecular oxidoreductases EC 6.4 Forming carbon–carbon bonds
EC 5.4 Intramolecular transferases EC 6.4.1 Ligases that form carbon–carbon bonds (only
EC 5.4.1 Transferring acyl groups sub-subclass identified to date)
EC 5.4.2 Phosphotransferases (phosphomutases) EC 6.5 Forming phosphoric-ester bonds
EC 5.4.3 Transferring amino groups EC 6.5.1 Ligases that form phosphoric-ester bonds (only
EC 5.4.4 Transferring hydroxy groups sub-subclass identified to date)
EC 5.4.99 Transferring other groups EC 6.6 Forming nitrogen–metal bonds
EC 5.5 Intramolecular lyases EC 6.6.1 Forming coordination complexes
EC 5.5.1 Intramolecular lyases (only sub-subclass
identified to date)
EC 5.99 Other isomerases
EC 5.99.1 Sole sub-subclass for isomerases that do not the list of enzymes is a continuing operation. The current
belong in the other subclasses database contains over 5500 enzymes, whereas in 1961 only
712 were recognised. Suggestions for enzymes that should be
included, or for revisions and corrections to existing entries,
can be submitted electronically using forms available through
groups may show different chain-length specificities for primary ExplorEnz, http://www.enzyme-database.org/forms.php. Alter-
aliphatic alcohols and also different inhibitor specificities. How- natively, material for all enzyme classes can be sent by e-mail
ever, because they all oxidise primary alcohols and have a strong or regular mail to Dr Andrew McDonald (Department of
preference towards NAD+ as the coenzyme, they are all grouped Biochemistry, Trinity College, Dublin 2, Ireland; E-mail:
together under the general heading of EC 1.1.1.1. Furthermore, amcdonld@tcd.ie). After these have been checked and con-
problems also arise from species differences; for example, EC sidered by the Nomenclature Committee as a whole, they
1.1.1.1 includes NAD+ -dependent alcohol dehydrogenases from are made available for a one-month period of public review
all species, although the mammalian liver and yeast enzymes, at http://www.enzyme-database.org/newenz.php before being
for example, are profoundly different in structure and behaviour. incorporated into the Enzyme Nomenclature database.
Only when isoenzymes have very different substrate specificities
might classification by function provide the whole solution. For
example, liver glucokinase is now recognised to be a member of References
the hexokinase family of isoenzymes (hexokinase type IV) and is
classified as a hexokinase (EC 2.7.1.1), whereas the name glucok- BioCyc Pathway/Genome Database Collection (2015) http://
inase (EC 2.7.1.2) is specifically recommended for the enzyme biocyc.org/
from invertebrates and microorganisms that has a high specificity BRENDA Enzyme Information System (2015) http://www.brenda-
enzymes.org/
for glucose. In other cases, this problem is addressed by link-
Berman HM, Kleywegt GJ, Nakamura H and Markley JL (2014) The
ing the electronic form of the enzyme list to other appropriate
Protein Data Bank archive as an open data resource. Journal of
databases, based on structural considerations.
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Caspi R, Altman T, Billington R, et al. (2014) The MetaCyc database
of metabolic pathways and enzymes and the BioCyc collec-
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(Database issue): D459–D471.
New enzymes and new functions of existing enzymes are being ChemSpider (2015) Chemical Structure Database. http://www.
discovered at a rapid pace and work on revising and expanding chemspider.com/

10 eLS © 2015, John Wiley & Sons, Ltd. www.els.net

 Enzyme Classification and Nomenclature

Dixon M and Webb EC (1958) Enzymes, pp. 183–227. London & ommendations of the Nomenclature Committee of the Interna-
New York: Longmans Green & Academic Press. tional Union of Biochemistry and Molecular Biology (IUBMB)
Eawag Biocatalysis/Biodegradation Database (2015) http:// http://www.ca.expasy.org/enzyme/
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IUPAC & IUBMB (2013) Nomenclature Recommendations. http:// Alberty RA, Cornish-Bowden A, Goldberg RN, et al. (2011) Recom-
www.chem.qmul.ac.uk/iupac/ mendations for terminology and databases for biochemical thermo-
Kanehisa M, Goto S and Sato Y (2014) Data, information, knowl- dynamics. Biophysical Chemistry 155: 89–103.
edge and principle: back to metabolism in KEGG. Nucleic Acids Boyce S and Tipton KF (2000) History of the enzyme nomenclature
Research 42 (Database issue): D199–D205. system. S. Boyce and K.F. Tipton. Bioinformatics 16: 34–40.
Kyoto Encyclopedia of Genes and Genomes, KEGG (2015). Copeland RA (2000) Enzymes: A Practical Introduction to Structure,
http://www.genome.ad.jp/kegg/ Mechanism, and Data Analysis. New York: Wiley-VCH Inc.
McDonald AG and Tipton KF (2014) Fifty-five years of enzyme clas- Kotera M, McDonald AG, Boyce S and Tipton KF (2008) Functional
sification: advances and difficulties. FEBS Journal 281: 583–592. group and substructure searching as a tool in metabolomics. PLoS
MEROPS (2014) The Peptidase Database. http://merops.sanger. One 3 (2): e1537.
ac.uk/ McDonald AG, Boyce S, Moss GP, et al. (2007) ExplorEnz: a
NIST Standard Reference Database on the Thermodynamics MySQL database of the IUBMB enzyme nomenclature. BMC
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gov:8080/enzyme/enzyme.html McDonald AG, Tipton KF and Boyce S (2009) Tracing metabolic
Protein Data Bank (PDB) (2015) http://www.rcsb.org/pdb/ pathways from enzyme data. Biochimica et Biophysica Acta 1794:
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(SIB) Enzyme nomenclature database primarily based on the rec-

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