Enzyme Nomenclature. Recommendations 1992
It is recommended that the term "peptidase" be used as synonymous with "peptide hydrolase" for any enzyme that hydrolyses peptide bonds. Peptidases are recommended to be further divided into "exopeptidases" that act only near a terminus of a polypeptide chain and "endopeptidases" that act internally in polypeptide chains. The types of exopeptidases and endopeptidases are described more fully below. The usage of "peptidase" now recommended is synonymous with "protease" as it was originally used  as a general term for both exopeptidases and endopeptidases, but it should be noted that previously, in Enzyme Nomenclature (1984), "peptidase" was restricted to the enzymes included in sub-subclasses EC 3.4.11-19, the exopeptidases. Also, the term "proteinase" used previously for the enzymes included in sub-subclasses EC 3.4.21-99 carried the same meaning as "endopeptidase", and has been replaced by "endopeptidase" for consistency.
The nomenclature of the peptidases is troublesome. Their specificity is commonly difficult to define, depending upon the nature of several amino acid residues around the peptide bond to be hydrolysed and also on the conformation of the substrate polypeptide chain. A classification involving the additional criterion of catalytic mechanism is therefore used.
Two sets of sub-subclasses of peptidases are recognised, those of the exopeptidases (EC 3.4.11-19) and those of the endopeptidases (EC 3.4.21-24 and EC 3.4.99). The exopeptidases act only near the ends of polypeptide chains, and those acting at a free N-terminus liberate a single amino-acid residue (aminopeptidases, EC 3.4.11), or a dipeptide or a tripeptide (dipeptidyl-peptidases and tripeptidyl-peptidases, EC 3.4.14). The exopeptidases acting at a free C-terminus liberate a single residue (carboxypeptidases, EC 3.4.16-18) or a dipeptide (peptidyl-dipeptidases, EC 3.4.15). The carboxypeptidases are allocated to four groups on the basis of catalytic mechanism: the serine-type carboxypeptidases (EC 3.4.16), the metallocarboxypeptidases (EC 3.4.17) and the cysteine-type carboxypeptidases (EC 3.4.18). Other exopeptidases are specific for dipeptides (dipeptidases, EC 3.4.13), or remove terminal residues that are substituted, cyclized or linked by isopeptide bonds (peptide linkages other than those of α-carboxyl to α-amino groups) (omega peptidases, 3.4.19).
The endopeptidases are divided into sub-subclasses on the basis of catalytic mechanism, and specificity is used only to identify individual enzymes within the groups. These are the sub-subclasses of serine endopeptidases (EC 3.4.21), cysteine endopeptidases (EC 3.4.22), aspartic endopeptidases (EC 3.4.23), metalloendopeptidases (EC 3.4.24) and threonine endopeptidases (EC 3.4.25). Endopeptidases that could not be assigned to any of the sub-subclasses EC 3.4.21-25 were listed in sub-subclass EC 3.4.99.
There are characteristic inhibitors of the members of each catalytic type of endopeptidase; to save space these have not been listed separately for each individual enzyme but are reviewed in  and . A general source of information on peptidases that similarly has not been cited for each individual enzyme is reference .
In describing the specificity of peptidases, use is made of a model in which the catalytic site is considered to be flanked on one or both sides by specificity subsites, each able to accommodate the sidechain of a single amino acid residue (based on ). These sites are numbered from the catalytic site, S1...Sn towards the N-terminus of the substrate, and S1'...Sn' towards the C-terminus. The residues they accommodate are numbered P1...Pn, and P1'...Pn', respectively, as follows:
Substrate: - P3 - P2 - P1 P1'- P2'- P3'-
Enzyme: - S3 - S2 - S1 * S1'- S2'- S3'-
In this representation, the catalytic site of the enzyme is marked *. The peptide bond cleaved (the scissile bond) is indicated by the symbol '' or a hyphen in the structural formula of the substrate, or a hyphen in the name of the enzyme. In describing the specificity of endopeptidases, the term "oligopeptidase" is used to refer to those that act only on substrates smaller than proteins.
Finally, in describing the specificity of endopeptidases, the term oligopeptidase' is used to refer to those that act optimally on substrates smaller than proteins.
Families of peptidases are referred to by use of the numbering system of Rawlings and Barrett [6, 7].
1. Grassmann, W. and Dyckerhoff, H. Über die Proteinase und die Polypeptidase der Hefe. 13. Abhandlung über Pflanzenproteasen in der von R. Willstätter und Mitarbeitern begonnenen Untersuchungsreihe. Hoppe-Seyler's Z. Physiol. Chem. 179 (1928) 41-78.
2. Barrett, A. J. and Salvesen, G. S. (eds) Proteinase Inhibitors, Elsevier Science Publishers, Amsterdam (1986).
3. Beynon, R. J. and Bond, J. S. Proteolytic Enzymes. A Practical Approach. IRL Press, Oxford (1989).
4. Barrett, A. J., Rawlings, N. D. and Woessner, J. F. (eds) Handbook of Proteolytic Enzymes, Academic Press, London (1998).
5. Berger, A. and Schechter, I. Mapping the active site of papain with the aid of peptide substrates and inhibitors. Philos. Trans. R. Soc. London, Ser. B:Biol. Sci. 257 (1970) 249-264.
6. Rawlings, N.D. and Barrett, A.J. In: Methods Enzymol. 244 (1994) 19-61 and 461-486; Methods Enzymol. 248 (1995) 105-120 and 183-228.
7. Rawlings, N. D. and Barrett, A. J. MEROPS: the peptidase database. Nucleic Acids Research 27 (1999) 325-331.
arphamenine A Arg[1ψ2,COCH2]Phe
arphamenine B Arg[1ψ2,COCH2]Tyr
bleomycin (See  and )
compound E-64 L-3-carboxy-2,3-trans-epoxypropanoyl-l-leucylamido-(4-guanidino)butane
cystatin the protein inhibitor of cysteine endopeptidases from chicken egg-white
globomycin (a cyclic peptide antibiotic, see )
pepstatin isovaleryl-L-valyl-L-valyl-4-amino-3-hydroxy-6-methylheptanoyl-L-alanyl-4-amino-3-hydroxy-6-methylhepatanoic acid
puromycin (See )
quisqualic acid 3-(3,5-dioxo-1,2,4-oxazadiazolidin-2-yl)Ala
1. Bycroft, B.W. (1987) Dictionary of antibiotics and related substances. Chapman and Hall, London
2. The Merck Index, 11th edition, Merck and Co, Inc., Rahway, 1989, p. 201.
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