Mechanisms and specificity of factor XIa and trypsin inhibition by protease nexin 2 and basic pancreatic trypsin inhibitor.

ABSTRACT: Factor XIa (FXIa) inhibition by protease nexin-2 (PN2KPI) was compared with trypsin inhibition by basic pancreatic trypsin inhibitor (BPTI). PN2KPI was a potent inhibitor of FXIa (K(i) ∼ 0.81 nM) and trypsin (K(i) ∼ 0.03 nM), but not of other coagulation proteases (thrombin, FVIIa, FIXa, FXa, FXIIa, plasmin, kallikrein, K(i) > 185 nM). PN2KPI was ∼775-fold more potent than BPTI in FXIa inhibition, but both exhibited similar potencies against trypsin. Studies of FXIa and trypsin inhibition by PN2KPI and BPTI and P1 site swap mutants (PN2KPI-R15 K, BPTI-K15 R) demonstrated that FXIa inhibition by PN2KPI and P1 site swap mutants and trypsin inhibition by PN2KPI and BPTI conform to a single-step, slow equilibration inhibitory mechanism, whereas FXIa-inhibition by BPTI follows a classical, comp

SUBMITTER: Navaneetham D 

PROVIDER: S-EPMC3031312 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature