Sriram Krishnaswamy
Professor of Pediatrics (Hematology)
Department: Pediatrics
Contact information
Research Institute / CHOP
310 Abramson
3516 Civic Center Blvd.
Philadelphia, PA 19104
310 Abramson
3516 Civic Center Blvd.
Philadelphia, PA 19104
Office: (215) 590-3346
Lab: (215) 590-2688
Lab: (215) 590-2688
Email:
skrishna@mail.med.upenn.edu
skrishna@mail.med.upenn.edu
Publications
Education:
BS (Biology)
Syracuse University, 1979.
Ph.D. (Biochemistry)
Syracuse University, 1984.
BS (Biology)
Syracuse University, 1979.
Ph.D. (Biochemistry)
Syracuse University, 1984.
Post-Graduate Training
Dept. of Biochemistry, University of Vermont, Burlington, VT, 1984-1987.
Permanent linkDept. of Biochemistry, University of Vermont, Burlington, VT, 1984-1987.
Description of Itmat Expertise
Enzymology, protein chemistry and physical biochemistry of blood coagulation. With relevance to the mission of ITMAT, we frequently work on novel inhibitors of coagulation that exploit the complexity of macromolecular interactions to achieve specificity for the coagulation enzymes.Selected Publications
Krishnaswamy, S.: Exosite-Driven Substrate Specificity and Function in Coagulation. J. Thromb. Haemost. 3: 54-67, 2005.Lu, G., Chhum, S. and Krishnaswamy, S.: The affinity of protein C for the thrombin-thrombomodulin complex is determined in a primary way by active site-dependent interactions. J. Biol. Chem. 280: 15471-15478, 2005.
Bianchini, E.P., Orcutt, S.J., Panizzi, P., Bock, P.E. and Krishnaswamy, S.: Ratcheting of the Substrate from the Zymogen to Proteinase Conformations Directs Sequential Cleavage of Prothrombin by Prothrombinase. Proc. Natl. Acad. Sci. U.S.A. 102: 10099-10104, 2005.
Cao, W., Krishnaswamy, S., Camire, R.M., Lenting, P.J. and Zheng, X.L.: Factor VIII accelerates proteolytic cleavage of von Willebrand factor by ADAMTS13. Proc. Natl. Acad. Sci. U.S.A. 105: 7416-7421, 2008.
Hacisalihoglu, A., Panizzi, P., Bock, P.E., Camire, R.M. and Krishnaswamy, S.: Restricted Active Site Docking by Enzyme-Bound Substrate Enforces the Ordered Cleavage of Prothrombin by Prothrombinase. J. Biol. Chem. 282: 32974 – 32982, 2007.
Kamath, P. and Krishnaswamy, S.: Fate of Membrane-Bound Reactants and Products during the Activation of Human Prothrombin by Prothrombinase. J. Biol. Chem. 283: 30164-30173, 2008.
Bradford, H.N., Miccuci, J.A. and Krishnaswamy, S.: Regulated Cleavage of Prothrombin by Prothrombinase. Repositioning a cleavage site reveals the unique kinetic behavior of the action of prothrombinase on its compound substrate. J. Biol. Chem. 285: 328-338, 2010.
Buddai, S.K., Lu, G., Layzer, J., Rusconi, C.P., Sullenger, B.A., Monroe, D. and Krishnaswamy, S.: An anticoagulant RNA aptamer that inhibits proteinase-cofactor interactions within prothrombinase. J. Biol. Chem. 285: 5212-5223, 2010.
Kamath, P., Huntington, J.A. and Krishnaswamy, S.: Ligand binding shuttles thrombin along a continuum of zymogen-like and proteinase-like states. J. Biol. Chem. 285: 28651-28658, 2010.
Kroh, H.K., Panizzi, P., Tchaikovski, S., Wei, N., Krishnaswamy, S. , Tans, G., Rosing, J., Furie, B., Furie, B.C. and Bock, P.E.: Active site-labeled prothrombin inhibits prothrombinase in vitro and thrombosis in vivo. J. Biol. Chem. 286: 23345-23356, 2011.
Bradford, H.N. and Krishnaswamy, S.: Meizothrombin is an Unexpectedly Zymogen-Like Variant of Thrombin. J. Biol.Chem. 287: 30914-30925, 2012.
Vadivel, K., Agah, S., Messer, A.S., Cascio, D., Bajaj, M.S., Krishnaswamy, S., Esmon, C.T., Padmanabhan, K. and Bajaj, S.P.: Structural and Functional Studies of -Carboxyglutamic Acid Domains of Factor VIIa and Activated Protein C: Role of Magnesium at Physiological Calcium. J. Mol. Biol. 425: 1961-1981, 2013.
Krishnaswamy, S.: The Transition of Prothrombin to Thrombin. J. Thromb. Hemostas. 11: 265-276, 2013.
Bradford, H.N., Orcutt, S.J. and Krishnaswamy, S.: Membrane Binding by Prothrombin Mediates its Constrained Presentation to Prothrombinase For Cleavage. J. Biol.Chem. in press, 2013.