Interscaffolding additivity: binding of P 1 variants of bovine pancreatic trypsin inhibitor to four serine proteases 1 1Edited by R. Huber

Tri-domain Bifunctional Inhibitor of Metallocarboxypeptidases A and Serine Proteases Isolated from Marine Annelid Sabellastarte magnifica

“…The important role of P1 threonine residue for elastase inhibition has been demonstrated by the BPTI mutants and is in agreement with our finding. The BPTI K15T mutant (with threonine at P1 position) showed a K i value 3 orders lower than natural BPTI (72).…”

“…Indeed, almost all Kunitz domains feature an alanine or glycine residue at this position (69,70), although other small side chain amino acid residues such as aspartate and serine have often been found at this position (67). In these reports it was shown that the presence of ␤-branched side chain residues such as valine causes a decrease in the energy of interaction with trypsin (also described for chymotrypsin), destabilizing the complex (72). Hence, the presence of lysine and glycine at P1 and P1Ј, respectively, of the third domain indicates a likely greater contribution to trypsin inhibition by this domain, a fact confirmed experimentally with the lower K i value determined for rSmCI D2-D3 in comparison with that obtained for rSmCI D1-D2.…”

“…However, this amino acid residue, which bears a ␤-branched side chain, has been described to bind to the S1 pocket of trypsin in a particularly weak mode (72). In contrast, studies involving the use of peptide combinatorial libraries have suggested that threonine could promote the inhibition of elastases (73).…”

Purification, characterization and molecular cloning of chymotrypsin inhibitor peptides from the venom of Burmese Daboia russelii siamensis

“…With regard to the competitive inhibition activity study, the P 1 residue in the center of the binding loop is particularly important and its variants have been shown to greatly alter the specificity and potential activity of these peptides [9,20]. The P 1 amino acid in many inhibitor families shows a high degree of variability [24].…”

Calculations of the binding affinities of protein-protein complexes with the fast multipole method

“…The bovine pancreatic trypsin inhibitor ͑BPTI͒-trypsin system where the crucial P 1 residue had been mutated to various residues, and the binding constants and mutated protein complex structures have been extensively documented. 32 The other two systems are well studied barnase-barstar complex 33 and the Streptomyces griseus proteinase B ͑SGPB͒-turkey ovomucoid third domain complex ͑OMTKY3͒.…”