Protease nomenclature

Alarcon JM, Malleret G, Touzani K, Vronskaya S, Ishii S, Kandel ER, Barco A (2004) Chromatin acetylation, memory, and LTP are impaired in CBP+/- mice a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration. Neuron 42(6) 947-959 Alnernri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, Yuan J (1996) Human lCElCED-3 protease nomenclature. Cell 87(2) 171... 

Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, Yuan J (1996), Human ICE/CED-3 protease nomenclature, Cell 87 171. 

Peptidases are enzymes that catalyse the hydrolysis of peptide bonds - the bonds between amino acids that are found in peptides and proteins. The terms protease , proteinase and proteolytic enzyme are synonymous, but strictly speaking can only be applied to peptidases that hydrolase bonds in proteins. Because there are many peptidases that act only on peptides, the term peptidase is recommended. Peptidases are included in subclass 3.4 of enzyme nomenclature [1,5]. 

Fig. 8. Organization of the kringle IV repeats in apo(a). It has been determined that kringle IV repeats, which vary in amino acid sequence from the identically repeated kringle sequence (kringle IV types 1 and 3-10), are highly variable in the population, ranging from less than 10 to greater than 50. The numbers in brackets below the boxes refer to the kringle nomenclature described in McLean et at. (M24). Sequences corresponding to apo(a) kringle V and protease domains are indicated by stippled and solid boxes, respectively.

The NC-IUBMB has introduced a number of changes in the terminology following the proposals made by Barrett, Rawlings and co-workers [7] [8]. The term peptidase should now be used as a synonym for peptide hydrolase and includes all enzymes that hydrolyze peptide bonds. Previously the term peptidases was restricted to exopeptidases . The terms peptidase and protease are now synonymous. For consistency with this nomenclature, the term proteinases has been replaced by endopeptidases . To complete this note on terminology, we remind the reader that the terms cysteine endopeptidases and aspartic endopeptidases were previously called thiol proteinases and acid or carboxyl proteinases , respectively [9],... 

Substrate specificity. Like most other enzymes, proteases display distinct preferences for certain substrates. These are often discussed using the nomenclature of Fig. 12-14. The substrate residue contributing the carbonyl of the amide group to be cleaved is designated Pj and residues toward the N terminus as P2, P3, etc., as is shown in Fig. 12-14. Residues toward the C terminus from the peptide linkage to be cleaved are designated P P etc. Chymotrypsin acts... 

Figure 12-14 Standard nomenclature used to define the residues Pl7 P2. .. toward the N terminus and Pj , P2. .. toward the C terminus of a peptide substrate for a protease. The corresponding subsites of the protease are designated Sj, S2. .. Sj, S. ...

FIGURE 2.1 Standard nomenclature for substrate residues and their corresponding binding sites on the protease. The subsites toward the N terminus of the substrate are called non-primed sites and are numbered SI to Sn, beginning with SI at the N terminal side of the scissile bond. The subsites toward the C terminus of the substrate are called primed sites and are numbered ST to Sn beginning with ST at the C terminal side of the scissile bond. The substrate residues that the enzymatic subsites accommodate are numbered PI to Pn and PT to Pn, respectively. 

Milk Coagulation. The first step in cheese manufacture is the coagulation of milk. Traditionally, this coagulation step is catalyzed by the enzyme rennet. Rennet is a saline extract of the 4th stomach of calves, usually slaughtered before they are 30 days old. The principal protease in rennet is rennin. In an attempt to avoid confusion with the hormone peptide renin, the International Enzyme Nomenclature Committee has assigned the name chymosin to the protease in calf rennet. During the growth of calves, chymosin is replaced by pepsin, the acid protease of the mature stomach. 

For reference to amino acid residues of prolylisomerase substrates and their corresponding enzyme subsites, we will adopt the nomenclature system of Schecter and Berger (1967) that is commonly used in protease chemistry. According to this system, if isomerization occurs at the Pi-P bond, and P, is Pro, the amino acid residues of the peptide substrate are named P - -P3-P2-Pi-P -P2 -P3 P , while the corresponding enzyme subsites are named S - S3-S2-Si-Sj -S2 -S3 - -Sn. 

The Gommission on Biochemical Nomenclature assigns enzyme numbers to 18 serine proteases in the 1972 edition of Enzyme Nomenclature (14). Seven are listed as having a trypsin-like specificity, i,e, their specific substrates have a positively charged lysine or arginine residue at Pi. Three are listed as having a chymotrypsin-like specificity, i.e., their specific substrates have residues of tryptophan, tyrosine, phenylalanine, or leucine at Pi, i,e, residues with bulky, hydrophobic side chains. Two enzymes have elastase-like specificities. They prefer a residue with... 

Figure 9.11. Specificity Nomenclature for Protease-Substrate Interactions. The potential sites of interaction of the substrate with the enzyme are designated P (shown in red), and corresponding binding sites on the enzyme are designated S. The scissile bond (also shown in red) is the reference point.

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