Philip Patston, D.Phil.,

Associate Professor,

Department of Oral Medicine and Diagnostic Sciences,

College of Dentistry,

University of Illinois at Chicago

 

Research Interests

My laboratory studies various aspects of the mechanism, regulation, structure, and function of the serpin family of proteins. Serpins are a large family of structurally related proteins many (but not all) of which are serine proteinase inhibitors.

An inhibitory serpin which is actively studied is C1-inhibitor, the only inhibitor of complement C1r and C1s proteinases, and an important inhibitor of plasma kallikrein and factor XIIa. Using Swiss-Model and Rasmol this is a modeled structure of cleaved C1-inhibitor. Currently we are investigating the role played by endothelial cells in regulating the inhibition of plasma kallikrein by C1-inhibitor, and using another serpin, alpha1-proteinase inhibitor, to design C1-inhibitor mimetics.

The non-inhibitory serpins under investigation are angiotensinogen and  thyroxine binding globulin.

Selected Publications

  1. PA Patston, P Gettins, J Beechem, and M Schapira (1991) Mechanism of serpin action. Evidence that C1-inhibitor functions as a suicide substrate. Biochemistry 30, 8876-8882
  2. K Skriver, WR Wikoff, PA Patston, F Tausk, M Schapira, AP Kaplan, and SC Bock (1991) Substrate properties of C1-inhibitor Ma (Alanine 434 to Glu). J. Biol. Chem. 266, 9216-9221
  3. P Gettins, PA Patston, and M Schapira (1993)The role of conformational change in serpin structure and function. Bioessays 15, 461-467
  4. PA Patston, RL Medcalf, Y Kourteva, and M Schapira (1993) C1-inhibitor-serine proteinase complexes and the biosynthesis of C1-inhibitor. Blood 82, 3371-3379
  5. PA Patston, and PGW Gettins (1994) A database of wild type and mutant recombinant serpins. Thromb. Haemost. 72, 166-179
  6. PA Patston, and M Schapira (1994) Low affinity heparin stimulates the inactivation of plasminogen activator inhibitor-1 by thrombin. Blood 84, 1164-1172
  7. PA Patston, PGW Gettins, and M Schapira (1994) Serpins are suicide substrates: Implications for the regulation of proteolytic pathways. Semin. Thromb. Hemost. 20, 410-416
  8. JA Huntington, PA Patston, and PGW Gettins (1995) S-ovalbumin, an ovalbumin conformer with properties analogous to those of loop-inserted serpins. Protein Sci. 4, 613-621
  9. PA Patston, J Hauert, M Michaud, and M Schapira (1995) Formation and properties of C1-inhibitor polymers. FEBS Lett. 368, 401-404
  10. PGW Gettins, PA Patston, and ST Olson (1996)Serpins. Structure, Function and Biology. R.G. Landes, pp220 (Book)
  11. PA Patston, and PGW Gettins (1996) Significance of secondary structure predictions on the reactive center loop region of serpins. A model for the folding of serpins into a metastable state. FEBS Lett. 383, 87-92
  12. PA Patston, and M Schapira (1997) Regulation of C1-inhibitor activity by binding to type IV collagen and heparin. Biochem. Biophys. Res. Commun. 230, 597-601
  13. ST Olson, R Swanson, PA Patston, and I Björk (1997) Apparent formation of sodium dodecyl sulfate-stable complexes between serpins and 3,4-dichloroisocoumarin-inactivated proteinases is due to regeneration of active proteinase from the inactivated enzyme. J. Biol. Chem. 272, 13338-13342
  14. M. Gauthier, and PA Patston (1997) Reactivation of C1-inhibitor polymers by denaturation and gel-filtration chromatography. Analyt. Biochem. 248, 228-233
  15. CE Chaillan-Huntington, PGW Gettins, JA Huntington, and PA Patston (1997) The P6-P2 region of serpins is critical for proteinase inhibition and complex stability. Biochemistry 36, 9562-9570
  16. CE Chaillan-Huntington, and PA Patston (1998)  Influence of the P5 residue on alpha-1-proteinase inhibitor mechanism. J. Biol. Chem. 273, 4569-4573
  17. J Hauert, PA Patston, and M Schapira (2000) C1-inhibitor cross-linking by tissue transglutaminase. J. Biol. Chem. 275, 14558-14562
  18. I Simonovic and, PA Patston (2000) The native metastable fold of C1-inhibitor is stabilized by disulfide bonds. Biochim. Biophys. Acta 1481, 97-102
  19. PA Patston (2000) Serpins and other serine protease inhibitors. Immunol. Today 21, 354 (Letter to the Editor)
  20. S Suda, PGW Gettins, and PA Patston (2000) Linkage between the hormone binding site and the reactive center loop of thyroxine binding globulin. Arch. Biochem. Biophys. 384, 31-36
  21. T Sulikowski, and PA Patston (2001) The inhibition of TNK-t-PA by C1-inhibitor. Blood. Coag. Fibrinolys. 12, 75-77
  22. A Ramaha, and PA Patston (2002) Release and degradation of angiotensin I and angiotensin II from angiotensinogen by neutrophil proteinases. Arch. Biochem. Biophys. 397, 77-83
  23. T Sulikowski, BA Bauer, and PA Patston (2002) Alpha1-Proteinase inhibitor reactive center loop mutants with specificity for kallikrein and C1s but not C1. Protein Sci., 11, 2230-2236
  24. EW Brown, S Ravindran, and PA Patston (2002) The reaction between plasmin and C1-inhibitor results in plasmin inhibition by the serpin mechanism. Blood Coag. Fibrinolys., 13, 711-714.
  25. A Ramaha, J. Célérier, and PA Patston (2003) Characterization of different high molecular weight angiotensinogen forms. Am. J. Hypertens. 16, 478-483.
  26. PA Patston, F Church, and ST Olson (2004) Ligand binding to serpins. Methods 32, 93-109.
Philip Patston, D.Phil.

Department of Oral Medicine and Diagnostic Sciences
University of Illinois-Chicago (MC 838)
801 South Paulina Street
Chicago, IL 60612

TEL: 312 996-8554; FAX: 312 355-2688; E-mail: patston@uic.edu

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Last Modified on January 20, 2004