Pro42 and Val45 of staphylokinase modulate intermolecular interactions of His43–Tyr44 pair and specificity of staphylokinase–plasmin activator complex

Abstract

Staphylokinase (SAK) forms a 1:1 stoichiometric complex with plasmin (Pm) and changes its substrate specificity to create a plasminogen (Pg) activator complex. The His43–Tyr44 pair of SAK resides within the active site cleft of the partner Pm and generates intermolecular contacts to confer Pg activator ability to the SAK–Pm bimolecular complex. Site-directed mutagenesis and molecular modeling studies unravelled that mutation at 42nd or 45th positions of SAK specifically disrupts cation-pi interaction of His43 with Trp215 of partner Pm within the active site, whereas pi–pi interaction of Tyr44 with Trp215 remain energetically favoured. Structured summary of protein interactionsPgbinds to SAK by surface plasmon resonance (View Interaction: 1, 2, 3)SAKenzymaticly reactsPg by enzymatic study (View Interaction: 1, 2, 3, 4, 5)