IDENTIFICATION OF RESIDUES LINKED TO THE SLOW-]FAST TRANSITION OF THROMBIN

Residues energetically linked to the allosteric transition of thrombin from its anticoagulant slow form to the procoagulant fast form have b een identified by site-directed mutagenesis, The energetics of recogni tion by the two forms of the enzyme were probed by using a synthetic c hromogenic substrate, fibrinogen, and hirudin, The thrombin residues E 39, W60d, E192, D221, and D222 are linked to the slow --> fast transit ion and are part of an ''allosteric core'' through which events origin ating at the Na+ binding loop propagate to other regions of the enzyme , The thrombin residues Y76, W96, W148, and R173 lie at the periphery of the allosteric core, affect recognition of fibrinogen and hirudin t o the same extent in both forms, and are not linked to the slow. --> f ast transition.