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The crystal structure of the complex of a bacterial alkaline serine proteinase,
subtilisin BPN', with its proteinaceous inhibitor SSI (Streptomyces subtilisin
inhibitor) was solved at 2.6 A resolution. Compared with other similar complexes
involving serine proteinases of the trypsin family, the present structure is
unique in several respects. (1) In addition to the usual antiparallel beta-sheet
involving the P1, P2 and P3 residues of the inhibitor, the P4, P5 and P6
residues form an antiparallel beta-sheet with a previously unnoticed chain
segment (residues 102 through 104, which was named the S4-6 site) of subtilisin
BPN'. (2) The S4-6 site does not exist in serine proteinases of the trypsin
family, whether of mammalian or microbial origin. (3) Global induced-fit
movement seems to occur on SSI: a channel-like structure in SSI where
hydrophobic side-chains are sandwiched between two lobes becomes about 2 A wider
upon complexing with subtilisin. (4) The complex is most probably a Michaelis
complex, as in most of the other complexes. (5) The main role of the "secondary
contact region" of SSI seems to be to support the reactive site loop ("primary
contact region"). Steric homology of the two contact regions between the
inhibitors of the SSI family and the pancreatic secretory trypsin
inhibitor-ovomucoid inhibitor family is so high that it seems to indicate
divergent evolutionary processes and to support the general notion as to the
relationship of prokaryotic and eukaryotic genes put forward by Doolittle (1978).
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