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Research ProgramStructural Biology
Research Interests
(Chemistry): Activation and Substrate Specificity of Thrombin and Factor XIII Probed by Structural and Kinetic Studies
Our research focus is on proteins involved in blood coagulation and related processes with an emphasis on the transglutaminase Factor XIII (FXIII) and the serine protease thrombin. FXIII catalyzes the formation of covalent crosslinks within the fibrin blood clot network. Thrombin converts fibrinogen into fibrin and activates such enzymes as FXIII and the protease activated receptors (PARs). Patients with cancer tend to experience abnormalities in blood coagulation and certain plasma proteins have been found in tumors and aid in anchoring. Furthermore, thrombin-activated PARs have been associated with hematogenous metastasis. In our studies, we utilize kinetic methods, solution NMR, hydrogen/deuterium exchange, MALDI-TOF mass spectrometry, and surface plasmon resonance measurements to examine the interplay of these different protein systems.
Education
Education/Training
B.A., Goucher College, Towson, MD, Chemistry, 1983-1987
Ph.D., University of Virginia, Charlottesville, Chemistry, 1987-1993
Postdoc, Cornell University, Ithaca, NY, Chemistry, 1992-1995
Research and Professional Experience
1992-1995
NIH Post-doctoral Fellow, Chemistry Department, Cornell University, Ithaca, NY
1995-1996
Post-doctoral Associate, Chemistry Department, Cornell University, Ithaca, NY
1996-1997
Research Associate, Chemistry Department, Cornell University, Ithaca, NY
1997-2003
Assistant Professor, Chemistry Dept., University of Louisville, Louisville, KY
2003-present
Associate Professor, Chemistry Dept., University of Louisville, Louisville, KY
Selected Awards and Professional Honors
1987
Phi Beta Kappa and Maryland American Chemical Society Student Award
1987
Stimson-Duvall Fellowship for Graduate Work from Goucher College
1989-1990
DuPont Graduate Fellowship, Chemistry Dept., University of Virginia
1992-1995
NIH Post-doctoral Fellowship (Heart, Lung, and Blood Institute)
Publications
Gibbs EJ, Maurer MC, Zhang JH, Reiff WM, Hill DT, Malicaka-Blaszkiewicz M, McKinnie RE, Liu H-Q, Pasternack RF. Interactions of porphyrins with purified DNA and more highly organized structures. J Inorganic Biochem 32:39-65, 1988.
Maurer MC, Sando JJ, Grisham CM. High affinity Ca2+ and substrate binding sites on PKC as determined by NMR spectroscopy. Biochemistry 31:7714-7721, 1992.
Maurer MC, Grisham CM, Sando JJ. Activation and inhibition of protein kinase C isozymes a and b by Gd3+. Arch Biochem Biophys 298:561-568, 1992.
Sando JJ, Maurer MC, Bolen EJ, Grisham CM. Role of cofactors in protein kinase C activation. Cell Signaling 4:595-609, 1992.
Saitoh H, Tomkiel J, Cooke CA, Ratrie III, H, Maurer M, Rothfield NF, Earnshaw WC. CENP-C, an autoantigen in scleroderma, is a component of the human inner kinetochore plate. Cell 70:115-125, 1992.
Earnshaw WC, Saitoh H, Tomkiel JE, Cooke CA, Barnat RL, Ratrie H, Maurer M, Rothfield NF. Molecular cloning and characterization of human centromere autoantigen CENP-C, a component of the inner kinetochore plate. Chromosomes Today 11:23-34, 1993.
DiBella EE, Maurer MC, Scheraga HA. Expression and folding of recombinant bovine prethrombin-2 and its activation to thrombin. J Biol Chem 270L:163-169, 1995.
Maurer MC, Peng J-L, An SS, Trosset J-Y, Henschen-Edman A, Scheraga HA. Structural examination of the influence of phosphorylation on the binding of fibrinopeptide A to bovine thrombin. Biochemistry 37:5888-5902, 1998.
Maurer MC, Trosset J-Y, Lester CC, DiBella EE, Scheraga HA. A new general approach for determining the solution structure of a ligand weakly bound to a receptor: Structure of a fibrinogen Aa-like peptide bound to thrombin (S195A) obtained using NOE distance constraints and an ECEPP/3 flexible docking program. Proteins. Structure, Function and Genetics 34:29-48, 1999.
Trumbo TA, Maurer MC. Examining thrombin hydrolysis of the Factor XIII activation peptide segment leads to a proposal for explaining the cardioprotective effects observed with the Factor XIII Val34Leu mutation. J Biol Chem 275:20627-20631, 2000.
Marinescu A, Cleary DB, Littlefield TR, Maurer MC. Structural features associated with the binding of glutamine-containing peptides to Factor XIII. Arch Biochem Biophys 406:9-20, 2002.
Cleary DB, Trumbo TA, Maurer MC. PAR4-like peptides binds to thrombin through an optimized interaction with the enzyme active site surface. Arch Biochem Biophys 403:179-188, 2002.
Turner BT, Jr, Maurer MC. Evaluating the roles of thrombin and calcium in the activation of coagulation Factor XIII using H/D exchange and MALDI-TOF MS. Biochemistry 41:7947-7954, 2002.
Trumbo TA, Maurer MC. Thrombin hydrolysis of V29 and V34 mutants of Factor XIII (28-41) reveals unique sites that regulate Factor XIII activation. Biochemistry 41:2859-2868, 2002.
Trumbo TA, Maurer MC. V34I and V34A substitutions within the Factor XIII activation peptide segment (28-41) affect interactions with the thrombin active site. Thrombosis Haemostasis 89:647-653, 2003.
Cleary DB, Ehringer WD, Maurer MC. Establishing the inhibitory effects of bradykinin on thrombin. Arch Biochem Biophys 410:96-106, 2003.
Isetti G, Maurer MC. N-terminal truncation of Factor XIII activation peptides (28-37) V34 and V34L does not hinder ability to interact with thrombin. Biochemistry 43:4150-4159, 2004.
Isetti G, Maurer MC. Probing thrombin's ability to accommodate a V34F substitution within the Factor XIII activation peptide segment (28-41). J Peptide Res 63:241-252, 2004.
Turner BT Jr, Sabo TM, Wilding D, Maurer MC. Mapping of factor XIII solvent accessibility as a function of activation state using chemical modification methods. Biochemistry 43(30):9755-65, 2004.
Phone: Coming soon.
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