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

AbstractStaphylokinase (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 interactionsPg binds to SAK by surface plasmon resonance (View Interaction: 1, 2, 3)SAK enzymaticly reacts Pg by enzymatic study (View Interaction: 1, 2, 3, 4, 5

Bharati Vidyapeeth's Institute of Computer Applications and Management

ABSTRAC

Intermolecular interactions in staphylokinase–plasmin(ogen) bimolecular complex: Function of His43 and Tyr44

AbstractStaphylokinase (SAK) forms a 1:1 stoichiometric complex with human plasmin (Pm) and switches its substrate specificity to generate a plasminogen (Pg) activator complex. Site-directed mutagenesis of SAKHis43 and SAKTyr44 demonstrated the crucial requirement of a positively charged and an aromatic residue, respectively, at these positions for optimal functioning of SAK–Pm activator complex. Molecular modeling studies further revealed the role of these residues in making cation–pi and pi–pi interactions with Trp215 of Pm and thus establishing the crucial intermolecular contacts within the active site cleft of the activator complex for the cofactor activity of SAK