Proposal for the mechanism of sequential prothrombin cleavage by prothrombinase. (A) The surface of pseutarin C is shown, with fVa in gray and fXa in cyan and the active site colored red. Prothrombin (yellow cartoon with semitransparent surface) is docked onto the side of fVa, with F1 (Gla-EGF1) binding to the C2 domain. The Pre1 portion of prothrombin (Pre1 surface electrostatic representation as inset) docks onto fVa in a manner that feeds Arg320 (blue) into the active site of fXa while keeping the 271 site (magenta) remote. (B) Cleavage of the 320 site causes the zymogen-to-protease conformational change in the catalytic domain of prothrombin (yielding the active intermediate meizothrombin; right inset) and an altered interaction with the K2 domain (indicated by change from yellow to green). The change in surface properties of meizothrombin (Meizo des F1; inset) result in an adjusted interaction with fVa, and the presentation of Arg271 to the active site of fXa.