Pro42 and Val45 of staphylokinase modulate intermolecular interactions of His43-Tyr44 pair and specificity of staphylokinase-plasmin activator complex.
Staphylokinase (SAK) forms a 1:1 stoichiometric complex with plasmin (Pm) and changes its substrate specificity to create a plasminogen (Pg) activator complex. The His(43)-Tyr(44) 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 His(43) with Trp(215) of partner Pm within the active site, whereas pi-pi interaction of Tyr(44) with Trp(215) remain energetically favoured.
Institute of Microbial Technology, CSIR, Chandigarh, India.
Satish
S
Singh
Ashish
Kanak L
KL
Dikshit
D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020134:Catalytic Domain; D005341:Fibrinolysin; D006639:Histidine / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D010960:Plasminogen Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011392:Proline / Q000378:metabolism*; D011487:Protein Conformation; D013379:Substrate Specificity; D020349:Surface Plasmon Resonance; D014443:Tyrosine / Q000378:metabolism*; D014633:Valine / Q000378:metabolism*
D001426:Bacterial Proteins; D046912:Multiprotein Complexes; D014443:Tyrosine; D006639:Histidine; D011392:Proline; D010960:Plasminogen Activators; D005341:Fibrinolysin; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus; D014633:Valine