Streptococcus virulence involves three-step plasminogen bindingMar. 20, 2015, 8:58 AM
Streptokinase is a virulence cofactor secreted by several species of streptococci bacteria that has become an important drug target because of its ability to trigger the dissolution of blood clots. It does that by binding to and activating plasminogen conformationally, and subsequently generating the fibrin-dissolving protease plasmin.
Now researchers at Vanderbilt University have shown for the first time that streptokinase binding to plasminogen is a three-step process. Using a stopped-flow spectrofluorometer, Ingrid Verhamme, Ph.D., and Paul Bock, Ph.D., showed that the first “encounter” complex formation was followed by two tightening conformational steps.
Their paper, published last fall in the Journal of Biological Chemistry, was selected as the best enzymology paper of 2014 by the journal, which is published by the American Society for Biochemistry and Molecular Biology.
The finding sheds new light on how group A and C streptococci can spread rapidly through tissues and the bloodstream. Streptokinase binding essentially “hijacks” plasminogen, resulting in local generation of plasmin and dissolution of the host’s protective fibrin barriers.
The research was supported in part by National Institutes of Health grant HL056181.