Peptide link cleavage

The mechanism by which the CPA-catalysed peptide-link cleavage occurs has drawn much research attention, and the pathway that is currently favoured is illustrated in a schematic form in Figure 28.23. In the first step, the peptide to be cleaved is manoeuvred into position close to the Zn + site the dominant substrate-protein interactions involved at this stage (Figure 28.23a) are ... 

The classification adopted by the Nomenclature Committee (NC) of the International Union of Biochemistry and Molecular Biology (IUBMB) divides peptidases into classes and subclasses according to the positional specificity in the cleavage of the peptide link of the substrate. The last publication of the complete printed version of the Enzyme Nomenclature was in 1992 [1][2], but a constantly updated version with supplements is available on the World Wide Web at http //www.chem.qmul.ac.uk/iubmb/enzyme/. Similarly, all available Protein Data Bank (PDB) entries classified as recommended by the NC-IUBMB can be found on the WWW at http //www.bio-chem.ucl.ac.uk/bsm/enzymes/. 

Fig. 19. Topography of the NBS cleavage of the six tyrosyl peptide links of native and

Carboxypeptidase A (CPA) is a pancreatic metaUoenz5Tne which catalyses the cleavage of a peptide link in a polypeptide chain. The site of cleavage is specific in two ways it occurs at the C-terminal amino acid (equation 28.22), and it exhibits a high selectivity for substrates in which the C-terminal amino acid contains a large aliphatic or Ph substituent. The latter arises from the presence, near to the active site, of a hydro-phobic pocket in the protein which is compatible with the accommodation of, for example, a Ph group (see below). 

Fig. 28.23 Schematic representation of the generally accepted mechanism for the CPA-catalysed cleavage of a C-terminal peptide link see Figure 28.24a for a more detailed diagram of the coordination sphere of the Zn + ion. The red line represents the protein chain only residues mentioned in the discussion are shown. The diagrams do not imply whether a mechanism is concerted or not.

Chymotrypsinogen, as synthesized by the pancreatic cells, is a single polypeptide chain which can maintain its native configuration if the disulphide links are reduced. Activation, by a series of peptide bond cleavages, eventually results in three separate polypeptide segments held together by disulphides, as indicated diagrammatically below. Destruction... 

Enzyme Cross-linking Cleavage of Peptide Hydrogel [14,... 

Mainly for these reasons, progress came to a halt, except for a report by Chi et al. 18) in 1965 who carried out alkaline hydrolysis of a Kearney type peptide and found unmodified urea as the only low molecular weight product from cleavage of the pyrimidine subnucleus of the peptide linked flavin. Hence, the peptide residue could not be linked to the flavin N(3) position. 

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