Serine protease cleavage site

The sensitivity of the relevant rate constants to the groups at the different sites is demonstrated in Table 7.1. The cleavage of amides in the active site of serine protease can be described formally by the two successive steps ... 

Figure 12-15 Schematic drawing of the active site of a cysteine protease of the papain family with a partial structure of an acyl-enzyme intermediate in green. The thiolate-imidazolium pair of Cys 25 His 159 lies deep in the substrate-binding cleft and bridges an interface between two major structural domains, just as the Ser His pair does in serine proteases (Fig. 12-10). This may facilitate small conformational changes during the catalytic cycle. Asn 175 provides a polarizable acceptor for positive charge, helping to stabilize the preformed ion pair, and allows easy transfer of an imidazolium proton to the product of substrate cleavage. The peptide NH of Cys 25 and the side chain of Gin 19 form an oxyanion hole.

Arg residue, but none, as yet, has been demonstrated. Trypsin cleavage of proinsulin generates small amounts (< 5%) of Arg-(A)-insulin, the form which is present in native insulin at very low levels (< 0.5%). In the absence of carboxypeptid-ase-B, both plasmin and trypsin tend to cleave Lys-Ala or Lys-Thr bonds in proinsulin, resulting in a partially degraded form of insulin that does not occur naturally [40], These serine proteases therefore seem to carry out the rare cleavage at single basic residue sites. 

C.A. Tsu, J.J. Perona, V. Scheuenber-GEB, C.W. Turck, C. S. Craik, The substrate spedfidty of Uca pugilator collage-nolytic serine protease 1 correlates with the bovine type 1 collagen cleavage sites. 

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