Proton Bridging in Catalysis by and Inhibition of Serine Proteases of the Blood Cascade System.

ABSTRACT: Inquiries into the participation of short hydrogen bonds in stabilizing transition states and intermediate states in the thrombin, factor Xa, plasmin and activated protein C-catalyzed reactions revealed that specific binding of effectors at S_n, n = 1-4 and S'_n, n = 1-3 and at remote exosites elicit complex patterns of hydrogen bonding and involve water networks. The methods employed that yielded these discoveries include; (1) kinetics, especially partial or full kinetic deuterium solvent isotope effects with short cognate substrates and also with the natural substrates, (2) kinetic and structural probes, particularly low-field high-resolution nuclear magnetic resonance (¹H NMR), of mechanism-based inhibitors and substrate-mimic peptide inhibitors. Short hyd

SUBMITTER: Kovach IM 

PROVIDER: S-EPMC8146069 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature