Enzyme Classification Introductory article Article Contents and Nomenclature • 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 Table 1 How to cite: represents the type of reaction catalysed, as illustrated in , 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 eLS © 2015, John Wiley & Sons, Ltd. www.els.net 1 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 + H2O = AH + BOH 4LyasesA= B + X − Y = A—B || XY 5 Isomerases A = B 6 Ligases A + B + NTP = A − B + NDP + PorA+ B + NTP = A − B + NMP + PP aAdapted 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 Accepted name rules of chemical nomenclature can write down its chemical 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. 2 eLS © 2015, John Wiley & Sons, Ltd. www.els.net 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.