Sinead Boyce, Trinity College, Dublin, Ireland
Keith F Tipton, Trinity College, Dublin, Ireland
Enzyme classification and nomenclature is a system that allows the unambiguous
identification of enzymes in terms of the reactions they catalyse. This relies on a numerical
system to class enzymes in groups according to the types of reaction catalysed andsystematic naming that describes the chemical reaction involved.
another phosphate-containing group through its phos-
The need for a rational nomenclature for enzymes can be
phate to another substrate, it is a phosphotransferase
seen from the plethora of unhelpful names for enzymes in
classified as EC 2.7. z.–, where z refers to the nature of the
the earlier literature. Only those who were directly involved
acceptor group, and so on. The detailed descriptions of the
might have known the difference between the old yellow
procedures for assigning enzymes to specific classes and
enzyme and the new yellow enzyme and what diaphorase,
subclasses and the rules for systematic enzyme names that
or for that matter DT-diaphorase, catalysed (try EC
have been approved by the IUBMB Nomenclature
1.6.99.1 and EC 1.8.1.4). Similarly, the reaction catalysed
Committee have been published in Enzyme Nomenclature
by rhodenese (thiosulfate sulfurtransferase: EC 2.8.1.1)
(1992). The account below has been adapted from the fuller
was not apparent from its name and use of the name
material in that source, which should be consulted if
urokinase to describe a peptidase (EC 3.4.21.73) is
confusing since the term kinase is usually used for enzymesthat transfer phosphate from ATP to another substrate.
In trying to bring some order to the chaotic situation of
enzyme nomenclature, Malcolm Dixon and Edwin Webb,
in 1958, took a step that was radically different from thatused in other branches of nomenclature by classifying
The basic layout of the classification for each enzyme is
enzymes in terms of the reactions they catalysed, rather
described below with some indication of the guidelines
than by their structures. This system has been adopted and
followed. Further details of the principles governing the
developed by the International Union of Biochemistry and
nomenclature of individual enzyme classes are given in the
Molecular Biology (IUBMB), through its Joint Nomen-
clature Committee with the International Union of Pure
The classification number, which is made
and Applied Chemistry (IUPAC) into the Enzyme
up of four digits, identifies the enzyme by the reaction
Nomenclature list of enzymes. This has been through
catalysed. This is also valuable for relating the information
several editions, the most recent being published in 1992.
This material is also made available in a modified form
through the SWISSPROT ENZYME on-line database.
for the enzyme is usually used, provided that it is
More recent additions and modifications to the list have
unambiguous. A number of generic words indicating
been published as supplements in the European Journal of
reaction types may be used in recommended names, but
Biochemistry and the most recent additions are available
not in the systematic names, e.g. dehydrogenase, reductase,
on-line (see Enzyme Supplement, 1999 in Further Reading
oxidase, peroxidase, kinase, tautomerase, deaminase, dehy-
dratase, etc. Where additional information is needed to
Detailed rules for naming and classifying enzymes have
make the reaction clear, a phrase indicating the reaction or
been formulated and it is a relatively easy matter to assign
a product may be added in parentheses after the second
an enzyme to an overall class and to give it a name that
part of the name, e.g. (ADP-forming), (dimerizing), (CoA-
describes what it does. For example, if it oxidizes some-
thing by reducing NAD(P), it is a dehydrogenase classified
as EC 1. x. 1. – , where the number x refers to the group
where possible, in the form of a ‘biochemical’ equation [I]:
oxidized: 1 for –CHOH–, 2 for aldehyde or ketone, etc.;
however, if it transfers a phosphate, diphosphate or
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This formulation gives no indication of the preferred
mitter norepinephrine (noradrenaline) has a systematic
equilibrium of the reaction or, indeed, whether it is readily
name of (R)-4-(2-amino-1-hydroxyethyl)-1,2-benzenediol,
reversible. In the case of reversible reactions, the direction
the antibiotic benzylpenicillin is [2S-(2a,5a, 6b)]-3,3-
chosen for the reaction and systematic name is the same for
dimethyl-7-oxo-6-[(phenylacetyl)amino]-4-thia-1-azabi-
all the enzymes in a given class, even if this direction has not
cyclo[3.2.0]heptane-2-carboxylic acid and aspirin is 2-
been demonstrated for all. Thus, systematic names are
based on this written reaction, even though only the reverse
The basic rules for writing down the systematic name of
of this may actually have been demonstrated experimen-
a compound are to take a basic, or root, structure or its
tally. Frequently, such biochemical equations are neither
derivative, for example benzoic acid is the derivative of the
root benzene in the case of aspirin. The substituents are
then written before it with the position of each substituent
for the enzyme. This is to be as comprehensive a list as
and any stereochemistry being identified. There are several
possible to aid searching for any specific enzyme. The
possible modifications of this procedure and it is possible to
inclusion of a name in this list does not mean that its use is
write more than one systematic name that is more-or-less
encouraged. In some cases where the same name has been
unambiguous (see for example, the alternative names that
given to more than one enzyme, this ambiguity will be
have been used for norepinephrine in the Merck Index).
Variations arise, for example, from the choice of root
compound and the order in which the substituents are
biguous terms what the enzyme actually catalyses.
written. Where systematic names are used, the enzyme
Systematic names consist of two parts. The first contains
classification system uses the IUPAC system, which uses
the name of the substrate or, in the case of a bimolecular
rather few root compounds and writes the substituents in
reaction, of the two substrates separated by a colon. The
alphabetical order (e.g. amino before hydroxy, before
second part, ending in -ase, indicates the nature of
methyl etc.). Chemists use fewer root structures than
the reaction. A number of generic words indicating a type
biochemists. For example, biochemists all know the amino
of reaction may be used in either recommended or
acid tryptophan and that it can be decarboxylated to
systematic names: oxidoreductase, oxygenase, transferase
tryptamine. Therefore, they have no trouble with naming
(with a prefix indicating the nature of the group
the hormone melatonin N-acetyl-5-methoxytryptamine.
transferred), hydrolase, lyase, racemase, epimerase, iso-
However, if a chemist does not accept tryptamine as a root
merase, mutase, ligase. Where additional information is
structure it would become N-[2-(5-methoxy-1H-indol-3-
needed to make the reaction clear, a phrase indicating the
yl)ethyl]acetamide. Because the enzyme classification
reaction or a product should be added in parentheses after
system is primarily designed for biochemists, the biochem-
the second part of the name, e.g. (ADP-forming), (dimeriz-
ical names are frequently used, where these are widely
known. However, collaboration with IUPAC ensures that
the systematic names can be readily found from these in
reaction catalysed, possible relationships to other enzymes,
species differences, metal-ion requirement, etc.
It should be noted that the systematic names of
Key references on the identification, nat-
norepinephrine and melatonin are single ‘words’, which
ure, properties and function of the enzyme. These have
can contain lots of hyphens in them and generally
been omitted from the examples below to save space.
systematic names are written as single ‘words’. Amongthe few exceptions to this general rule are acids, includingphosphates, as shown by the examples of penicillin andaspirin, where ‘acid’ is written as a separate word. Similarly
creatine phosphate is written as two words, although it ispossible to write the compound as a single word by
Although a detailed description of chemical nomenclature
rearranging the name to phosphocreatine. An example of
is beyond the scope of this article, some comments are
such rearrangement is the name 6-phosphofructokinase
necessary because the fearsome names used are often
for the enzyme (EC 2.7.1.11) that catalyses the reaction:
difficult for a biochemist 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 nomenclaturecan write down its chemical structure and formula from it.
Note that the term bisphosphate is used here rather than
Therefore, it must be unambiguous both in terms of all the
diphosphate. In order to avoid confusion, diphosphate is
chemical groups that make up the compound, how and
used only for cases where the two phosphates are linked
where they are linked together and the compound’s
together (as in adenosine diphosphate; ADP) whereas
stereochemistry. This does lead to names that are not
bisphosphates have the two phosphates attached to
much help for general use, for example, the neurotrans-
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When a substrate name has two words there is a
The second figure in the code number of the oxidor-
potential problem using them in enzyme names. Glucose-
eductases denotes the type of group in the hydrogen-donor
6-phosphate 1-dehydrogenase (EC 1.1.1.49) catalyses the
substrate that is oxidized or reduced. The third number
denotes the hydrogen acceptor: 1 denotes NAD(P), 2 acytochrome, 3 molecular oxygen, 4 a disulfide, 5 a quinone
d-glucose 6-phosphate 1 NADP = d-glucono-1,5-lac-
or similar compound, 6 a nitrogenous group, 7 an iron–
sulfur protein and 8 a flavin. The number 99 is used for allother acceptors. This group contains a number of enzymes
but in order to indicate that the substrate oxidized is
that have been shown to work with synthetic acceptors,
glucose 6-phosphate, not just phosphate, an extra hyphen
such as 2,6-dichloroindophenol or phenazine methosul-
fate, but where the physiological acceptor is unknown. It is
In denoting stereochemistry, the IUPAC rules prefer the
intended that they should be transferred to more descrip-
R- and S- system and this is generally used for enzyme
tive sub-subclasses when the natural acceptor is identified.
nomenclature. However, in the case of sugars and amino
For subclasses 1.13 and 1.14, a different classification
acids, the d- and l- designations are so well known that
scheme is used since these enzymes catalyse the incorpora-
they are followed in the enzyme list. The use of italics in
tion of oxygen into the substrate. The recommended names
chemical names can at first seem rather odd, but the
are generally monooxygenase or dioxygenase, depending
simplest way of thinking about it is to think how one would
on whether one or two atoms of oxygen are incorporated
look up the name of a compound in an index, for example
into the substance oxidized. The sub-subclasses are
N-acetyl-5-methoxytryptamine would be found by search-
ing through A for acetyl not N for N-acetyl. Clearly the
Table 1 summarizes the structure of Class 1.
same applies to R- and S-isomers. Therefore, the italic canbe taken to mean ‘do not bother to look under this letter in
any index’. Having adopted this way of doing things, it islogical also to use italics for these when they occur in the
middle of a name. The exceptions to this general rule are
Recommended name: l-iditol 2-dehydrogenase
the d- and l- designations, which are not italicized,
Reaction: l-iditol 1 NAD 5 l-sorbose 1 NADH2
however, these are written, by convention, in a smaller
The above summary glosses over many of the complex-
Systematic name: l-iditol:NAD 2-oxidoreductase
ities of systematic chemical nomenclature and fuller details
Comments: Also acts on d-glucitol (giving d-fructose)
of the rules and their application can be found in A Guide to
and other closely related sugar alcohols.
IUPAC Nomenclature of Organic Compounds (1994) .
Reaction:l-lysine 1 NADPH2 1 O2 5 N6-hydroxy-l-
Systematic name: l-lysine, NADPH2:oxygen oxidore-
This class contains the enzymes catalysing oxidation
Comments: A flavoprotein (FAD). The enzyme from
reactions. Since the oxidation of one group must be
strain EN 222 of E. coli is highly specific for l-lysine; l-
accompanied by the reduction of another, they are grouped
ornithine and l-homolysine are, for example, not sub-
together as oxidoreductases. The systematic enzyme name
strates. A lysine monooxygenase (EC 1.13.12.10) from this
is in the form donor:acceptor oxidoreductase. The substrate
organism has been reported to catalyse the same hydro-
that is being oxidized is regarded as being the hydrogen
xylation without the involvement of NAD(P)H
donor. The recommended name is commonly donor
dehydrogenase. Although the term reductase is sometimesused as an alternative, it is important to remember that the
recommended name does not define the equilibriumposition of the reaction or the net direction of flux through
These enzymes transfer a group from one substrate (the
the enzyme in vivo. Indeed, in some cases, an enzyme within
donor) to another (the acceptor) according to the general
a metabolic pathway can proceed in a thermodynamically
unfavoured direction because of the effective removal of
one of the reactants. The term donor oxidase is used onlywhen O2 is the acceptor.
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Table 1 Class 1.–.–.– Oxidorectuses
1. 1.–.– Acting on the CH–OH group of donors
1. 1. 2.– With a cytochrome as acceptor
1. 1. 5.– With a quinone or similar compound as acceptor
1. 2. –.– Acting on the aldehyde or oxo group of donors
1. 2. 2.– With a cytochrome as acceptor
1. 2. 7.– With an iron–sulfur protein as acceptor
1. 3.–.– Acting on the CH–CH group of donors
1. 3. 2.– With a cytochrome as acceptor
1. 3. 5.– With a quinone or related compound as acceptor
1. 3. 7.– With an iron–sulfur protein as acceptor
1. 4.–.– Acting on the CH–NH2 group of donors
1. 4. 2.– With a cytochrome as acceptor
1. 4. 7.– With an iron–sulfur protein as acceptor
1. 5.–.– Acting on the CH–NH group of donors
1. 5. 5.– With a quinone or similar compound as acceptor
1. 6. 2.– With a cytochrome as acceptor
1. 6. 5.– With a quinone or similar compound as acceptor
1. 6. 6.– With a nitrogenous group as acceptor
1. 7.–.– Acting on other nitrogenous compounds as donors
1. 7. 2.– With a cytochrome as acceptor
1. 7. 7.– With an iron–sulfur protein as acceptor
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Table 1 – continued
1. 8.–.– Acting on a sulfur group of donors
1. 8. 2.– With a cytochrome as acceptor
1. 8. 5.– With a quinone or similar compound as acceptor
1. 8. 7.– With an iron–sulfur protein as acceptor
1. 9.–.– Acting on a haem group of donors
1. 9. 6.– With a nitrogenous group as acceptor
1.10.–.– Acting on diphenols and related substances as donors
1.10. 2.– With a cytochrome as acceptor
1.11.–.– Acting on a peroxide as acceptor (peroxidases)
1.11.1.– A single subclass containing the peroxidases
1.12. 2.– With a cytochrome as acceptor
1.13.–.– Acting on single donors with incorporation of molecular oxygen
1.13.11.– With incorporation of two atoms of oxygen
1.13.12.– With incorporation of one atom of oxygen
1.13.99.– Miscellaneous (requires further characterization)
1.14.–.– Acting on paired donors with incorporation of molecular oxygen
1.14.11.– With 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors
1.14.12.– With NADH2 or NADPH2 as one donor, and incorporation of two atoms of oxygen into one donor1.14.13.– With NADH2 or NADPH2 as one donor, and incorporation of one atom of oxygen1.14.14.– With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
1.14.15.– With a reduced iron–sulfur protein as one donor, and incorporation of one atom of oxygen
1.14.16.– With reduced pteridine as one donor, and incorporation of one atom of oxygen
1.14.17.– With ascorbate as one donor, and incorporation of one atom of oxygen
1.14.18.– With another compound as one donor, and incorporation of one atom of oxygen
1.14.99.– Miscellaneous (requires further characterization)
1.15.–.– Acting on superoxide radicals as acceptor
1.18.–.– Acting on reduced ferredoxin as donor
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Table 1 – continued
1.19.–.– Acting on reduced flavodoxin as donor
Note: The Nomenclature Committee has accepted a recommendation that nicotinamide-adenine dinucleotide and nicotinamide-adenine dinucle-
otide phosphate should be abbreviated to NAD and NADP, respectively, rather than NAD+ and NADP+, as used previously. In addition toavoiding the erroneous implication that these two compounds will be positively charged at physiological pH values, the reasons for this aregiven in the Newsletter (1996). The reduced forms of these coenzymes are written as NADH and NADPH , rather than NADH and NADPH.
The systematic name is in the form donor:acceptor group-
transferase. The recommended names are normally formed
Sometimes transferase reactions can be considered in
different ways; for example, the general reaction shown
Reaction: S-adenosyl-l-methionine 1 3-hexaprenyl-
above may be regarded as a transfer of the group Y from X
4,5-dihydroxybenzoate 5 S-adenosyl-l-homocysteine
to Z, and would therefore be termed a Y-transferase.
1 3-hexaprenyl-4-hydroxy-5-methoxybenzoate
However, it could also be considered as a breaking of the
X–Y bond by the introduction of Z. For example, where Z
represents phosphate, the process is often referred to as
phosphorolysis and the enzyme catalysing the reaction as a
Systematic name: S-adenosyl-l-methionine:3-hexapre-
phosphorylase. For systematic purposes, these enzymes are
nyl-4,5-dihydroxylate O-methyltransferase
Comments: Involved in the pathway of ubiquinone
The aminotransferase (transaminase) reactions involve
synthesis. This enzyme has been listed as EC 2.1.1.64 in
some sequence databases; but that enzyme catalyses a
containing a carbonyl group, in exchange for the 5 O of
R1–CHNH2–R2 1 R3–CO–R4 = R1–CO–
These enzymes catalyse the hydrolytic cleavage of bonds
such as C–O, C–N, C–C and some other bonds, includingphosphoric anhydride bonds. The overlapping specificitiesof many of these enzymes make it difficult to formulate
Thus, the reaction could be regarded as being an oxidative
general rules that are applicable to all members of this
deamination of the donor (e.g. an amino acid) linked to the
class. The systematic name usually takes the form substrate
reductive amination of the acceptor (e.g. oxo acid).
X-hydrolase, where X is the group removed by hydrolysis.
Therefore these enzymes might be classified as oxidor-
The recommended name is, in many cases, formed by the
eductases. However, since the unique distinctive feature of
name of the substrate with the suffix -ase. It is understood
the reaction is the transfer of the amino group, these
that the name of the substrate with this suffix means a
enzymes are classified as amino transferases (subclass
Hydrolytic enzymes might be classified as transferases,
The second figure in the code number of the transferases
since hydrolysis itself can be regarded as transfer of a
denotes the general nature of the group transferred (a one-
specific group to water as the acceptor. Yet, in most cases,
carbon group, 2.1; aldehydic or ketonic group, 2.2; acyl
the reaction with water as the acceptor was discovered
group, 2.3, etc.) and the third number further specifies that
earlier and is considered as the main physiological function
group (methyltransferase, 2.1.1; formyltransferase, 2.1.2,
of the enzyme. This is why such enzymes are classified as
etc.). The exception is the case of the enzymes transferring
hydrolases rather than as transferases.
phosphorus-containing groups (subclass 2.7), where the
The second number indicates the nature of the bond
third number specifies the nature of the acceptor group.
hydrolysed, and the third normally specifies the nature of
Table 2 summarizes the structure of Class 2.
the substrate, e.g. in the esterases the carboxylic ester
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hydrolases (3.1.1), thiolester hydrolases (3.1.2), phosphoric
(3.4.11–19), with the third figure also depending on the
monoester hydrolases (3.1.3); in the glycosidases, the O-
catalytic mechanism. A complete list of the peptidases is
glycosidases (3.2.1), N-glycosidases (3.2.2), and so on.
now available on-line (see Peptidases, 1998 in Further
The peptidases (formerly called peptide hydrolases;
Class 3.4.–) cannot be accommodated within this general
Subclasses 3.9 - 3.11, which each contain only one or two
scheme. It is not even possible to give unambiguous
known enzymes, only contain one sub-subclass each,
systematic names because of variable specificities and great
denoted by the figure 1 (e.g. 3.9.1.1, 3.10.1, 3.10.1.2 etc).
similarities between the actions of different peptidases. The
Table 3 summarizes the structure of Class 3.
enzymes are grouped into two sets of sub-subclasses, theendopeptidases (3.4.21–24 and 3.4.99) and exopeptidases
Recommended name: 4-hydroxybenzoyl-CoA thioesterase
Reaction: 4-hydroxybenzoyl-CoA 1 H2O 5 4-hydro-
2. 1. –.– Transferring one-carbon groups
Systematic name: 4-hydroxybenzoyl-CoA hydrolase
2. 1. 2. – Hydroxymethyl-, formyl- and related transferases
Comments: This enzyme is part of the bacterial 2,4-
2. 1. 3. – Carboxyl- and carbamoyltransferases
2. 2. –.– Transferring aldehyde or ketone residues
2. 2. 1. – a single subclass containing the transaldolases
Reaction: Broad proteolytic activity. With small-mole-
cule substrates and inhibitors, the major determinant of
specificity is P2, which is preferably Leu, Met 4 Phe, and
Other names: cathepsin O and cathepsin X (both
misleading, having been used for other enzymes); Cathe-
2. 4.99. – Transferring other glycosyl groups
Comments: Prominently expressed in mammalian os-
2. 5. –.– Transferring alkyl or aryl groups, other than methyl
teoclasts, and believed to play a role in bone resorption. In
2. 5. 1. – A single subclass that includes a rather mixed
NOTE: The specificity of peptidases may be described in
terms of a sequence of amino acid residues on either side of
2. 6. –.– Transferring nitrogenous groups
the peptide bond that is cleaved (scissile bond), which is
2. 6. 1. – Transaminases (aminotransferases)
2. 6.99. – Transferring other nitrogenous groups
2 2 2 2 P3 2 P2 2 P1P1’ 2 P2’ 2 P3’ 2 C-terminus
2. 7. –.– Transferring phosphorus-containing groups
2. 7. 1. – Phosphotransferases with an alcohol group as
2. 7. 2. – Phosphotransferases with a carboxyl group as
These enzymes cleave C–C, C–O, C–N and other bonds by
means other than hydrolysis or oxidation. They differ from
2. 7. 3. – Phosphotransferases with a nitrogenous group as
other enzymes in that two substrates are involved in one
reaction direction but only one in the other. When acting
2. 7. 4. – Phosphotransferases with a phosphate group as
on the single substrate, a molecule is eliminated leaving
double bonds or rings. The systematic name is formed
according to the pattern substrate group-lyase. The hyphen
is an important part of the name and, to avoid confusion,
2. 7. 8. – Transferases for other substituted phosphate
should not be omitted, e.g. hydro-lyase not ‘hydrolyase’. In
the recommended names, expressions like decarboxylase or
2. 7. 9. – Phosphotransferases with paired acceptors
aldolase (in case of elimination of CO2 or aldehyde,
2. 8. –.– Transferring sulfur-containing groups
respectively) are used. Dehydratase is used for those
enzymes catalysing the elimination of water. In cases
where the reverse reaction is much more important, or the
only one demonstrated, synthase (not synthetase) may be
2. 9. –.– Transferring selenium-containing groups
used in the name. Although the term synthetase has
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Table 3 Class 3.–.–.–. Hydrolases
3.1. 1. – Carboxylic ester hydrolases 3.1. 2. – Thiolester hydrolases 3.1. 3. – Phosphoric monoester hydrolases 3.1. 4. – Phosphoric diester hydrolases 3.1. 5. – Triphosphoric monoester hydrolases 3.1. 6. – Sulfuric ester hydrolases 3.1. 7. – Diphosphoric monoester hydrolases 3.1. 8. – Phosphoric triester hydrolases 3.1.11. – Exodeoxyribonucleases producing 5′-phosphomonoesters 3.1.13. – Exoribonucleases producing 5′-phosphomonoesters 3.1.14. – Exoribonucleases producing other than 5′-phosphomonoesters 3.1.15. – Exonucleases active with either ribo- or deoxyribonucleic acids and producing 5′-phosphomonoesters 3.1.16. – Exonucleases active with either ribo- or deoxyribonucleic acids and producing other than 5′-phosphomonoesters 3.1.21. – Endodeoxyribonucleases producing 5′-phosphomonoesters 3.1.22. – Endodeoxyribonucleases producing other than 5′-phosphomonoesters 3.1.25. – Site-specific endodeoxyribonucleases specific for altered bases 3.1.26. – Endoribonucleases producing 5′-phosphomonoesters 3.1.27. – Endoribonucleases producing other than 5′-phosphomonoesters 3.1.30. – Endonucleases active with either ribo- or deoxyribonucleic acid and producing 5′-phosphomonoesters 3.1.31. – Endonucleases active with either ribo- or deoxyribonucleic acid and producing other than 5′-phosphomonoesters
3.2. 1. – Hydrolysing O-glycosyl compounds 3.2. 2. – Hydrolysing N-glycosyl compounds 3.2. 3. – Hydrolysing S-glycosyl compounds
3.3. 1. – Thioether hydrolases 3.3. 2. – Ether hydrolases
3. 4. –.– Acting on peptide bonds (peptidase)
3.4.11. – Aminopeptidases 3.4.13. – Dipeptidases 3.4.14. – Dipeptidyl-peptidases and tripeptidyl-peptidases 3.4.15. – Peptidyl-dipeptidases 3.4.16. – Serine-type carboxypeptidases 3.4.17. – Metallocarboxypeptidases 3.4.18. – Cysteine-type carboxypeptidases 3.4.19. – Omega peptidases 3.4.21. – Serine endopeptidases 3.4.22. – Cysteine endopeptidases 3.4.23. – Aspartic endopeptidases 3.4.24. – Metalloendopeptidases 3.4.99. – Endopeptidases of unknown catalytic mechanism
3. 5. –.– Acting on carbon–nitrogen bonds, other than peptide bonds
3.5. 1. – In linear amides 3.5. 2. – In cyclic amides 3.5. 3. – In linear amidines 3.5. 4. – In cyclic amidines 3.5. 5. – In nitriles 3.5.99. – In other compounds
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Table 3 – continued
3.6. 1. – In phosphorus-containing anhydrides
3.6. 2. – In sulfonyl-containing anhydrides
3. 7. –.– Acting on carbon–carbon bonds
3. 9. –.– Acting on phosphorus–nitrogen bonds3.10. –.– Acting on sulfur–nitrogen bonds3.11. –.– Acting on carbon–phosphorus bonds3.12. –.– Acting on sulfur–sulfur bonds
sometimes been used in the names of enzymes from this
indicates the bond broken: 4.1 are carbon–carbon lyases,
class, that use is discouraged in order to prevent confusion
4.2 are carbon–oxygen lyases, and so on. The third figure
with enzymes from Class 6 (see below).
gives further information on the group eliminated (e.g.
Various subclasses of the lyases include pyridoxal-
phosphate enzymes that catalyse the elimination of a b-
Table 4 summarizes the structure of Class 4.
or g-substituent from an a-amino acid, followed by a
replacement of this substituent by some other group. In the
overall replacement reaction, no unsaturated end productis formed; therefore, these enzymes might formally be
classified as alkyltransferases (EC 2.5.1.-). However, there
Reaction: 2-hydroxyisobutyronitrile 5 cyanide 1
is ample evidence that the replacement is a two-step
reaction involving the transient formation of enzyme-
Other name(s): hydroxynitrile lyase; oxynitrilase
bound a,b- (or b,g-)unsaturated amino acids. According to
Systematic name: 2-hydroxyisobutyronitrile acetone-
the rule that the first reaction is indicative for classification,
these enzymes are correctly classified as lyases. Examples
Comments: The enzyme from Hevea (rubber tree) and
are tryptophan synthase (EC 4.2.1.20) and cystathionine b-
Manihot spp. (cassava) accepts aliphatic and aromatic
lyase (EC 4.2.1.22). The second figure in the code number
hydroxynitriles, unlike EC 4.1.2.11, which does not act onaliphatic
Table 4 Class 4. –.–.– Lyases
(acetone cyanohydrin) is liberated by glycosidase actionon linamarin
These enzymes catalyse geometric or structural changes
within one molecule. According to the type of isomerism
involved they may be called racemases, epimerases, cis–
trans-isomerases, isomerases, tautomerases, mutases or
cycloisomerases. The second number denotes the type of
isomerism involved, and the third number the type ofsubstrate. In some cases, the reaction involves an
intermolecular oxidoreduction, but since the donor and
acceptor groups are in the same molecule they are classified
as isomerases rather than oxidoreductases, even though
they may contain firmly bound NAD or NADP.
4. 3.99 – Other carbon–nitrogen-lyases
Table 5 summarizes the structure of Class 5.
Recommended name: a-methylacyl-CoA racemase
ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net
Table 5 Class 5. –.–.– Isomerases
5. 1. 1. – Acting on amino acids and derivatives
Recommended name: 4-chlorobenzoate-CoA ligase
Reaction: 4-chlorobenzoate 1 CoA 1 ATP 5 4-
5. 1. 2. – Acting on hydroxy acids and derivatives
5. 1. 3. – Acting on carbohydrates and derivatives
Systematic name: 4-chlorobenzoate : CoA ligase
Comments: Requires Mg2 1 . This enzyme is part of the
5. 2. –.– cis–trans-Isomerases
bacterial 2,4-dichlorobenzoate degradation pathway.
5. 3. –.– Intramolecular oxidoreductases
5. 3. 1. – Interconverting aldoses and ketoses
5. 3. 2. – Interconverting keto- and enol-groups
5. 3. 3. – Transposing C=C bonds5. 3. 4. – Transposing S–S bonds
Isoenzymes may not be easily accommodated in any
5. 3.99. – Other intramolecular oxidoreductases
system of classification simply in terms of reaction
5. 4. –.– Intramolecular transferases (mutases)
catalysed. For example, there are about 20 differentisoenzymes of alcohol dehydrogenase in human liver.
These have been organized into broad classes in terms of
5. 4. 2. – Phosphotransferases (phosphomutases)
their electrophoretic mobilities and, more precisely, in
terms of their sequences and genetic origin. These classes
show very different chain-length specificities for primary
aliphatic alcohols and also different inhibitor specificities.
However, since they all oxidize primary alcohols and havea strong preference towards NAD as the coenzyme, theyare all grouped together under the general heading of EC1.1.1.1. Furthermore, problems also arise from species
Reaction: (2S)-2-methylacyl-CoA 5 (2R)-2-methyla-
differences; for example, class EC 1.1.1.1 includes NAD-
dependent alcohol dehydrogenases from all species,
Systematic name: 2-methylacyl-CoA 2-epimerase
although the mammalian liver and yeast enzymes, for
Comments: a-methyl-branched acyl-CoA derivatives
example, are profoundly different in structure and
with chain lengths of more than C10 are substrates. Also
behaviour. Only when isoenzymes have very different
active towards some aromatic compounds (e.g. ibuprofen)
substrate specificities might classification by function
and bile acid intermediates, such as trihydroxycoprosta-
provide the whole solution. For example, liver glucokinase
is now recognized to be a member of the hexokinase familyof isoenzymes (hexokinase type IV) and is classified as ahexokinase (EC 2.7.1.1), whereas the name glucokinase
These enzymes catalyse the joining together (ligating) of
two molecules with the concomitant hydrolysis of a
6. 1. –.– Forming carbon–oxygen bonds
diphosphate bond in ATP or a similar triphosphate. The
6. 1. 1. – Ligases forming aminoacyl-tRNA and related
systematic enzyme name takes the form A:B ligase (XDP-
or XMP-forming). The recommended name often takes the
6. 2. –.– Forming carbon–sulfur bonds
form A–B ligase. Sometimes the name synthase is used for
the recommended name to emphasize the synthetic nature
6. 3. –.– Forming carbon–nitrogen bonds
of the reaction, which can also be helpful if the reaction is
6. 3. 1. – Acid–ammonia (or amine) ligases (amide
complex. The name synthetase is also sometimes used
instead of synthase in the names of enzymes in this class.
6. 3. 2. – Acid–amino-acid ligases (peptide synthases)
The second figure in the code number indicates the bond
formed: 6.1 for C–O bonds (enzymes acylating tRNA), 6.2
6. 3. 4. – Other carbon–nitrogen ligases
for C–S bonds (acyl-CoA derivatives), etc. Sub-subclasses
6. 3. 5. – Carbon–nitrogen ligases with glutamine as
are only in use in the C–N ligases (6.3), which include the
amide synthases (6.3.1), the peptide synthases (6.3.2),
6. 4. –.– Forming carbon–carbon bonds
enzymes forming heterocyclic rings (6.3.3), etc.
6. 5. –.– Forming phosphoric ester bonds
Table 6 summarizes the structure of Class 6.
ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net
(EC 2.7.1.2) is specifically recommended for the enzyme
from invertebrates and microorganisms that has a highspecificity for glucose. In other cases, this problem is being
Alberty RA, Cornish-Bowden A, Gibson QH et al. (1996) Recommen-
dations for nomenclature and tables in biochemical thermodynamics.
addressed by linking the electronic form of the enzyme list
European Journal of Biochemistry 240: 1–14.
to other appropriate databases, based on structural
Dixon M and Webb EC (1958) Enzymes, pp. 183–227. London:
Enzyme Nomenclature (1992) Recommendations of the Nomenclature
Committee of the International Union of Biochemistry and Molecular
Biology on the Nomenclature and Classification of Enzymes. NewYork: Academic Press.
Enzyme Supplements (1999) Prepared for the NC-IUBMB by Tipton
New enzymes and new functions of existing enzymes are
KF and Boyce S. [http://www.chem.qmw.ac.uk/iubmb/enzyme/]
being discovered at a rapid pace and work on revising and
IUBMB Nomenclature Committee Enzyme Nomenclature. Recom-
expanding the list of enzymes is a continuing operation.
mendations of the Nomenclature Committee of the International
Suggestions for enzymes that should be included, or for
revisions and corrections to existing entries can be
Newsletter (1996) of the IUPAC-IUBMB Joint Commission on
submitted electronically using forms available through
Biochemical Nomenclature (JCBN) and Nomenclature Committee
the IUBMB Nomenclature Committee Enzyme Nomen-
of IUBMB (NC-IUBMB). Archives of Biochemistry and Biophysics
clature or SWISSPROT ENZYME home pages. Alter-
(1997) 344: 242–252; Biochemical Journal (1997) 327: 311–319;
natively, material for all enzyme classes except the
Chemistry International (1997) 19: 116–119; European Journal of
peptidases (Class 3.4. –.–) can be sent by e-mail or regular
Biochemistry (1997) 247: 733–739; Glycoconjugate Journal (1998) 15:
mail to Dr Sinead Boyce (Department of Biochemistry,
637–647. Also available on-line at [http://www.chem.qmw.ac.uk/iubmb/newsletter/]
Trinity College, Dublin 2, Ireland; E-mail: [email protected]).
Panico R, Richer J-C Powell WH (1994) A Guide to IUPAC
Material relating to the peptidases should be sent to Dr
Nomenclature of Organic Compounds. Oxford: Blackwell Science.
Alan J. Barrett (Peptidase Laboratory, Department of
Peptidases (1998) Prepared for the NC-IUBMB by Barrett AJ, Bond JS,
Immunulogy, Babraham Institute, Babraham CB2 4AT,
Fiedler F et al. [http://www.chem.qmw.ac.uk/iubmb/enzyme/EC34/]
UK; E-mail; [email protected]). After these have
SWISSPROT ENZYME. Swiss Institute of Bioinformatics (SIB)
been checked and considered by the Nomenclature
Enzyme nomenclature database primarily based on the recommenda-
Committee as a whole, they are incorporated into the
tions of the Nomenclature Committee of the International Union ofBiochemistry and Molecular Biology (IUBMB) [http://www.expa-
Enzyme Nomenclature database, which is being prepared
ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net
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