Research Topics
| Steven OlsonSummaryAffiliation: University of Illinois at Chicago Country: USA Publications
Research Grants
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Detail Information
Publications
Specificity and selectivity profile of EP217609: a new neutralizable dual-action anticoagulant that targets thrombin and factor XaSteven T Olson
Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, 60612, USA
Blood 119:2187-95. 2012..These findings demonstrate the superior anticoagulant efficacy and rapid avidin neutralizability of EP217609 compared with anticoagulants that target thrombin or factor Xa alone...- Molecular mechanisms of antithrombin-heparin regulation of blood clotting proteinases. A paradigm for understanding proteinase regulation by serpin family protein proteinase inhibitorsSteven T Olson
Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Chicago, IL 60612, USA
Biochimie 92:1587-96. 2010.... 
Resolution of Michaelis complex, acylation, and conformational change steps in the reactions of the serpin, plasminogen activator inhibitor-1, with tissue plasminogen activator and trypsinS T Olson
Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Chicago, Illinois 60612, USA
Biochemistry 40:11742-56. 2001....- Heparin activates antithrombin anticoagulant function by generating new interaction sites (exosites) for blood clotting proteinasesSteven T Olson
Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, 60612, USA
Trends Cardiovasc Med 12:331-8. 2002.... - Identification of critical molecular interactions mediating heparin activation of antithrombin: implications for the design of improved heparin anticoagulantsSteven T Olson
Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, 60612 7213 USA
Trends Cardiovasc Med 12:198-205. 2002.... - Specificity and reactive loop length requirements for crmA inhibition of serine proteasesLisa D Tesch
Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, Chicago, IL 60612, USA
Protein Sci 14:533-42. 2005..These results indicate that crmA inhibits serine proteases by the established serpin conformational trapping mechanism, but is unusual in inhibiting through either of two adjacent reactive sites... - Characterization of the conformational alterations, reduced anticoagulant activity, and enhanced antiangiogenic activity of prelatent antithrombinBenjamin Richard
Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Chicago, IL 60612, USA
J Biol Chem 283:14417-29. 2008..Together, these results demonstrate that limited conformational alterations of antithrombin that modestly reduce anticoagulant activity are sufficient to generate antiangiogenic activity... - Deletion of P1 arginine in a novel antithrombin variant (antithrombin London) abolishes inhibitory activity but enhances heparin affinity and is associated with early onset thrombosisSrikumar M Raja
Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 60612, USA
J Biol Chem 278:13688-95. 2003.... - The heparin-binding site of antithrombin is crucial for antiangiogenic activityWeiqing Zhang
Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Rm 530E, Dentistry M C 860, 801 S Paulina St, Chicago, IL 60612, USA
Blood 106:1621-8. 2005.... - Localization of an antithrombin exosite that promotes rapid inhibition of factors Xa and IXa dependent on heparin activation of the serpinGonzalo Izaguirre
Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois 60612, USA
J Biol Chem 278:51433-40. 2003..These findings suggest that antithrombin exosites responsible for enhancing the rates of factor Xa and factor IXa inhibition in the conformationally activated inhibitor lie in strand 3 of beta-sheet C of the serpin... - Residues Tyr253 and Glu255 in strand 3 of beta-sheet C of antithrombin are key determinants of an exosite made accessible by heparin activation to promote rapid inhibition of factors Xa and IXaGonzalo Izaguirre
Center for Molecular Biology of Oral Diseases, University of Illinois, Chicago, Illinois 60612, USA
J Biol Chem 281:13424-32. 2006..Together, these results indicate that Tyr253 and Glu255 are key exosite determinants responsible for promoting the reactions of conformationally activated antithrombin with both factor Xa and factor IXa... - Mechanism by which exosites promote the inhibition of blood coagulation proteases by heparin-activated antithrombinGonzalo Izaguirre
Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Chicago, Illinois 60612, USA
J Biol Chem 282:33609-22. 2007..Together these results show that exosites generated by heparin activation of antithrombin function both to promote the formation of an initial antithrombin-protease Michaelis complex and to favor the subsequent acylation of this complex... - Serpin-ligand interactionsPhilip A Patston
Department of Oral Medicine and Diagnostic Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA
Methods 32:93-109. 2004..We summarize here the different approaches that have been used to identify serpin ligands and the many methods that have been used to characterize the interactions of these ligands with their cognate serpins... - Antiangiogenic antithrombin down-regulates the expression of the proangiogenic heparan sulfate proteoglycan, perlecan, in endothelial cellsWeiqing Zhang
Center for Molecular Biology of Oral Diseases and Department of Biochemistry and Molecualr Genetics, University of Illinois at Chicago, 60612, USA
Blood 103:1185-91. 2004.... - Basis for the specificity and activation of the serpin protein Z-dependent proteinase inhibitor (ZPI) as an inhibitor of membrane-associated factor XaXin Huang
Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Chicago, Illinois 60607, USA
J Biol Chem 285:20399-409. 2010.... - Serine and cysteine proteases are translocated to similar extents upon formation of covalent complexes with serpins. Fluorescence perturbation and fluorescence resonance energy transfer mapping of the protease binding site in CrmA complexes with granzyme Richard Swanson
Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois, Chicago, Illinois 60612, USA
J Biol Chem 282:2305-13. 2007.... - Antiangiogenic antithrombin blocks the heparan sulfate-dependent binding of proangiogenic growth factors to their endothelial cell receptors: evidence for differential binding of antiangiogenic and anticoagulant forms of antithrombin to proangiogenic hepaWeiqing Zhang
Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Chicago, Illinois 60612, USA
J Biol Chem 281:37302-10. 2006..Moreover, the inability of native antithrombin to bind this co-receptor implies that native and conformationally altered forms of antithrombin differentially bind proangiogenic heparan sulfate domains... - Antiangiogenic antithrombin induces global changes in the gene expression profile of endothelial cellsWeiqing Zhang
Center for Molecular Biology of Oral Diseases and Department of Oral Biology, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois 60612, USA
Cancer Res 66:5047-55. 2006.... 
Activation of antithrombin as a factor IXa and Xa inhibitor involves mitigation of repression rather than positive enhancementPeter G W Gettins
Department of Biochemistry and Molecular Genetics, and Center for Structural Biology, University of Illinois at Chicago, IL 60612 4316, USA
FEBS Lett 583:3397-400. 2009....- The signature 3-O-sulfo group of the anticoagulant heparin sequence is critical for heparin binding to antithrombin but is not required for allosteric activationBenjamin Richard
Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Chicago, Illinois 60612, USA
J Biol Chem 284:27054-64. 2009.... - Kinetic characterization of the protein Z-dependent protease inhibitor reaction with blood coagulation factor XaXin Huang
Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Chicago, Illinois 60612, USA
J Biol Chem 283:29770-83. 2008..Together our findings show that ZPI functions like other serpins to regulate the activity of FXa but in a manner uniquely dependent on protein Z, procoagulant membranes, and pH... - Engineering functional antithrombin exosites in alpha1-proteinase inhibitor that specifically promote the inhibition of factor Xa and factor IXaGonzalo Izaguirre
Center for Molecular Biology of Oral Diseases, University of Illinois, Chicago, Illinois 60612, USA
J Biol Chem 284:1550-8. 2009..Together, these results show that a specific and selective inhibitor of factor Xa can be engineered by incorporating factor Xa exosite and reactive site recognition determinants in a serpin... - Use of fluorescence resonance energy transfer to study serpin-proteinase interactionsPeter G W Gettins
Department of Biochemistry and Molecular Genetics, M C 669, University of Illinois at Chicago, Chicago, IL 60607, USA
Methods 32:110-9. 2004..However, care must be taken to ensure that measurements made represent sufficient overdetermination that the answer obtained is unambiguous... - Exosite determinants of serpin specificityPeter G W Gettins
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60612, USA
J Biol Chem 284:20441-5. 2009..A frequent theme is down-regulation of inhibitory activity unless the exosite(s) are engaged. In addition, the use of exosites by maspin and plasminogen activator inhibitor-1 to indirectly affect proteolytic processes is considered... - Accelerating ability of synthetic oligosaccharides on antithrombin inhibition of proteinases of the clotting and fibrinolytic systems. Comparison with heparin and low-molecular-weight heparinSteven T Olson
Center for Molecular Biology of Oral Diseases, University of Illinois-Chicago, Illinois, USA
Thromb Haemost 92:929-39. 2004..These results establish the proteinase targets of heparin derivatives currently used in or considered for thrombosis therapy and give new insights into the mechanism of heparin acceleration of antithrombin inhibition of proteinases... - Heparin and calcium ions dramatically enhance antithrombin reactivity with factor IXa by generating new interaction exositesTina Bedsted
Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois 60612, USA
Biochemistry 42:8143-52. 2003..These results together with our previous findings demonstrate that exosites are responsible for the unusual specificity of antithrombin and heparin for three clotting proteases with quite distinct substrate specificities... - Cytokine response modifier a inhibition of initiator caspases results in covalent complex formation and dissociation of the caspase tetramerJózsef Dobó
Department of Biochemistry and Molecular Genetics, University of Illinois, 900 S Ashland, Chicago, IL 60607, USA
J Biol Chem 281:38781-90. 2006.... - Serine protease inhibitor 6-deficient mice have increased neutrophil immunity to Pseudomonas aeruginosaManling Zhang
Department of Pathology, University of Chicago, Chicago, IL 60637, USA
J Immunol 179:4390-6. 2007..Therefore, deficiency in a weak intracellular inhibitor of NE results in an acute inflammatory response that protects from P. aeruginosa but does not cause lung disease... - Phosphorylation of serine 256 suppresses transactivation by FKHR (FOXO1) by multiple mechanisms. Direct and indirect effects on nuclear/cytoplasmic shuttling and DNA bindingXiaohui Zhang
Department of Medicine, College of Medicine, University of Illinois, Chicago, Illinois 60612, USA
J Biol Chem 277:45276-84. 2002..Binding is rapid and reversible, providing an opportunity for the phosphorylation of Ser-256 and subsequent phosphorylation of Thr-24 and Ser-319 and nuclear exclusion of FKHR... - Importance of lysine 125 for heparin binding and activation of antithrombinSophia Schedin-Weiss
Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences, Uppsala
Biochemistry 41:4779-88. 2002..These effects are exerted by interactions of Lys125 with the nonreducing end of the heparin pentasaccharide... - The heparin binding properties of heparin cofactor II suggest an antithrombin-like activation mechanismSteven T Olson
University of Cambridge, Department of Haematology, Division of Structural Medicine, Thrombosis Research Unit, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Cambridge CB2 2XY, United Kingdom
J Biol Chem 279:50267-73. 2004..We conclude that the heparin-binding mechanism of HCII is closely analogous to that of AT and that the induced fit mechanism suggests the potential design or discovery of specific HCII agonists... - Roles of N-terminal region residues Lys11, Arg13, and Arg24 of antithrombin in heparin recognition and in promotion and stabilization of the heparin-induced conformational changeSophia Schedin-Weiss
Department of Molecular Biosciences, Swedish University of Agricultural Sciences, Uppsala Biomedical Center, SE-751 23 Uppsala, Sweden
Biochemistry 43:675-83. 2004.... - Contribution of basic residues of the autolysis loop to the substrate and inhibitor specificity of factor IXaLikui Yang
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Missouri 63104, USA
J Biol Chem 278:25032-8. 2003.... - Specificity of the basic side chains of Lys114, Lys125, and Arg129 of antithrombin in heparin bindingSophia Schedin-Weiss
Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences, Uppsala Biomedical Center, Box 575, SE 751 23 Uppsala, Sweden
Biochemistry 41:12369-76. 2002.... - Binding of exosite ligands to human thrombin. Re-evaluation of allosteric linkage between thrombin exosites I and IIIngrid M Verhamme
Department of Pathology, Vanderbilt University School of Medicine, Medical Center North, Nashville, TN 37232, USA
J Biol Chem 277:6788-98. 2002..The results indicate significant, ligand-specific allosteric coupling between thrombin exosites I and II and catalytic site perturbations but insignificant inter-exosite thermodynamic linkage... - Importance of tryptophan 49 of antithrombin in heparin binding and conformational activationBernhard H Monien
Department of Medicinal Chemistry and Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia 23298-0540, USA
Biochemistry 44:11660-8. 2005..This destabilization could be accounted for by the disruption of a network of interactions involving Trp49, Glu50, and Lys53 of helix A and Ser112 of helix P, which stabilizes the activated conformation... - Antithrombin III phenylalanines 122 and 121 contribute to its high affinity for heparin and its conformational activationMohamad Aman Jairajpuri
Departments of Medicine and Bioengineering, Health Science Center, University of Utah, 50 N Medical Drive, Salt Lake City, UT 84132, USA
J Biol Chem 278:15941-50. 2003....
Research Grants
- MOLECULAR BASIS OF BLOOD COAGULATION REGULATIONSteven Olson; Fiscal Year: 2009..This understanding is expected to facilitate the rational design of a new generation of anticoagulant and antitumor drugs for the treatment and prevention of cardiovascular diseases and cancer. ..
- MOLECULAR BASIS OF BLOOD COAGULATION REGULATIONSteven Olson; Fiscal Year: 2007..This understanding is expected to facilitate the rational design of a new generation of anticoagulant and antitumor drugs for the treatment and prevention of cardiovascular diseases and cancer. ..
- MOLECULAR BASIS OF BLOOD COAGULATION REGULATIONSteven Olson; Fiscal Year: 2005....
- MOLECULAR BASIS OF BLOOD COAGULATION REGULATSteven Olson; Fiscal Year: 2001..These studies should also provide a rational basis for the design of recombinant antithrombins or synthetic heparins with tailor-made antithrombotic activity. ..
- Structural Basis of Serpin Function and RegulationSteven Olson; Fiscal Year: 2009..The proposed studies will utilize mutagenesis, fluorescence, NMR and X-ray crystallography and thermodynamic and kinetic approaches to characterize serpin-protease and serpin-ligand interactions. ..