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Photo of  Paul R. Rosevear, PhD

Paul R. Rosevear, PhD

Professor

Molecular & Cellular Biosciences | College of Medicine

Education/Credentials
  • Research Associate : Brandeis University (Biophysics, NMR Spectroscopy)
  • Research Fellowship: The Johns Hopkins School of Medicine (Biological NMR, Protein structure/function)
  • Postdoctoral fellowship: Fox Chase Cancer Center (Mechanistic enzymology and biological NMR)
  • Doctoral Degree: Michigan State University (Biochemistry)
  • Master's Degree: Old Dominion University (Chemistry)
  • Bachelor's Degree: Old Dominion University (Chemistry)
Contact Information
Research Interests

My major interest is the use of nuclear magnetic resonance (NMR) to solve biological and physiological problems.  Elucidating the relationships between protein structure and function has been a major research interest over the last 20 years.  Currently we are interested in the role that natively disordered regions play in protein recognition and binding.  In particular, we are interested in disorder-to-order transitions that occur with phosphoryltions and other post-translatinal modificatio...

Peer Reviewed Publications

Michalek, A.J., Gulick, J., Robbins, J. Howarth, J.W., Rosevear, P.R. and Warshaw, D.M. 2013. Phosphorylation modulates mechanical stability of the cardiac myosin binding protein-C motif Biophysical Journal-Biophysical Letters, 104 2, 442

Howarth, Jack W; Ramisetti, Srinivas; Nolan, Kristof; Sadayappan, Sakthivel; Rosevear, Paul R 2012. Structural insight into unique cardiac myosin-binding protein-C motif: a partially folded domain. The Journal of biological chemistry, 287 11, 8254-62

Millard, Ronald W; Rosevear, Paul R 2012. Metabolomics: seeking a unique biomarker signature for coronary artery syndromes. Journal of the American College of Cardiology, 59 18, 1642-4

Sadayappan, Sakthivel; Finley, Natosha; Howarth, Jack W; Osinska, Hanna; Klevitsky, Raisa; Lorenz, John N; Rosevear, Paul R; Robbins, Jeffrey 2008. Role of the acidic N' region of cardiac troponin I in regulating myocardial function. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 22 4, 1246-57

Solaro, R John; Rosevear, Paul; Kobayashi, Tomoyoshi 2008. The unique functions of cardiac troponin I in the control of cardiac muscle contraction and relaxation. Biochemical and biophysical research communications, 369 1, 82-7

Howarth, Jack W; Meller, Jarek; Solaro, R John; Trewhella, Jill; Rosevear, Paul R 2007. Phosphorylation-dependent conformational transition of the cardiac specific N-extension of troponin I in cardiac troponin. Journal of molecular biology, 373 3, 706-22

Sakthivel, Sadayappan; Finley, Natosha L; Rosevear, Paul R; Lorenz, John N; Gulick, James; Kim, Scott; VanBuren, Peter; Martin, Lisa A; Robbins, Jeffrey 2005. In vivo and in vitro analysis of cardiac troponin I phosphorylation. The Journal of biological chemistry, 280 1, 703-14

Finley, Natosha L; Howarth, Jack W; Rosevear, Paul R 2004. Structure of the Mg2+-loaded C-lobe of cardiac troponin C bound to the N-domain of cardiac troponin I: comparison with the Ca2+-loaded structure. Biochemistry, 43 36, 11371-9

Finley, Natosha L; Rosevear, Paul R 2004. Introduction of negative charge mimicking protein kinase C phosphorylation of cardiac troponin I. Effects on cardiac troponin C. The Journal of biological chemistry, 279 52, 54833-40

Sorsa, Tia; Pollesello, Piero; Rosevear, Paul R; Drakenberg, Torbjörn; Kilpeläinen, Ilkka 2004. Stereoselective binding of levosimendan to cardiac troponin C causes Ca2+-sensitization. European journal of pharmacology, 486 1, 1-8

Heller, William T; Finley, Natosha L; Dong, Wen-Ji; Timmins, Peter; Cheung, Herbert C; Rosevear, Paul R; Trewhella, Jill 2003. Small-angle neutron scattering with contrast variation reveals spatial relationships between the three subunits in the ternary cardiac troponin complex and the effects of troponin I phosphorylation. Biochemistry, 42 25, 7790-800

Rosevear, Paul R; Finley, Natosha 2003. Molecular mechanism of levosimendan action: an update. Journal of molecular and cellular cardiology, 35 9, 1011-5

Dvoretsky, Alex; Abusamhadneh, Ekram M; Howarth, Jack W; Rosevear, Paul R 2002. Solution structure of calcium-saturated cardiac troponin C bound to cardiac troponin I. The Journal of biological chemistry, 277 41, 38565-70

Dvoretsky, Alex; Gaponenko, Vadim; Rosevear, Paul R 2002. Derivation of structural restraints using a thiol-reactive chelator. FEBS letters, 528 1-3, 189-92

Heller, William T; Abusamhadneh, Ekram; Finley, Natosha; Rosevear, Paul R; Trewhella, Jill 2002. The solution structure of a cardiac troponin C-troponin I-troponin T complex shows a somewhat compact troponin C interacting with an extended troponin I-troponin T component. Biochemistry, 41 52, 15654-63

Abbott, M B; Dong, W J; Dvoretsky, A; DaGue, B; Caprioli, R M; Cheung, H C; Rosevear, P R 2001. Modulation of cardiac troponin C-cardiac troponin I regulatory interactions by the amino-terminus of cardiac troponin I. Biochemistry, 40 20, 5992-6001

Abusamhadneh, E; Abbott, M B; Dvoretsky, A; Finley, N; Sasi, S; Rosevear, P R 2001. Interaction of bepridil with the cardiac troponin C/troponin I complex. FEBS letters, 506 1, 51-4

Sorsa, T; Heikkinen, S; Abbott, M B; Abusamhadneh, E; Laakso, T; Tilgmann, C; Serimaa, R; Annila, A; Rosevear, P R; Drakenberg, T; Pollesello, P; Kilpelainen, I 2001. Binding of levosimendan, a calcium sensitizer, to cardiac troponin C. The Journal of biological chemistry, 276 12, 9337-43

Abbott, M B; Dvoretsky, A; Gaponenko, V; Rosevear, P R 2000. Cardiac troponin I inhibitory peptide: location of interaction sites on troponin C. FEBS letters, 469 2-3, 168-72

Abbott, M B; Gaponenko, V; Abusamhadneh, E; Finley, N; Li, G; Dvoretsky, A; Rance, M; Solaro, R J; Rosevear, P R 2000. Regulatory domain conformational exchange and linker region flexibility in cardiac troponin C bound to cardiac troponin I. The Journal of biological chemistry, 275 27, 20610-7

Finley, N; Dvoretsky, A; Rosevear, P R 2000. Magnesium-calcium exchange in cardiac troponin C bound to cardiac troponin I. Journal of molecular and cellular cardiology, 32 8, 1439-46

Gaponenko, V; Dvoretsky, A; Walsby, C; Hoffman, B M; Rosevear, P R 2000. Calculation of z-coordinates and orientational restraints using a metal binding tag. Biochemistry, 39 49, 15217-24

Gaponenko, V; Howarth, J W; Columbus, L; Gasmi-Seabrook, G; Yuan, J; Hubbell, W L; Rosevear, P R 2000. Protein global fold determination using site-directed spin and isotope labeling. Protein science : a publication of the Protein Society, 9 2, 302-9

Permi, P; Rosevear, P R; Annila, A 2000. A set of HNCO-based experiments for measurement of residual dipolar couplings in 15N, 13C, (2H)-labeled proteins. Journal of biomolecular NMR, 17 1, 43-54

Finley, N; Abbott, M B; Abusamhadneh, E; Gaponenko, V; Dong, W; Gasmi-Seabrook, G; Howarth, J W; Rance, M; Solaro, R J; Cheung, H C; Rosevear, P R 1999. NMR analysis of cardiac troponin C-troponin I complexes: effects of phosphorylation. FEBS letters, 453 1-2, 107-12

Gaponenko, V; Abusamhadneh, E; Abbott, M B; Finley, N; Gasmi-Seabrook, G; Solaro, R J; Rance, M; Rosevear, P R 1999. Effects of troponin I phosphorylation on conformational exchange in the regulatory domain of cardiac troponin C. The Journal of biological chemistry, 274 24, 16681-4

Gasmi-Seabrook, G M; Howarth, J W; Finley, N; Abusamhadneh, E; Gaponenko, V; Brito, R M; Solaro, R J; Rosevear, P R 1999. Solution structures of the C-terminal domain of cardiac troponin C free and bound to the N-terminal domain of cardiac troponin I. Biochemistry, 38 26, 8313-22

Howarth, J W; Krudy, G A; Lin, X; Putkey, J A; Rosevear, P R 1995. An NMR and spin label study of the effects of binding calcium and troponin I inhibitory peptide to cardiac troponin C. Protein science : a publication of the Protein Society, 4 4, 671-80

Kleerekoper, Q; Howarth, J W; Guo, X; Solaro, R J; Rosevear, P R 1995. Cardiac troponin I induced conformational changes in cardiac troponin C as monitored by NMR using site-directed spin and isotope labeling. Biochemistry, 34 41, 13343-52

Zhou, L; Rosevear, P R 1995. Mutation of the carboxy terminal zinc finger of E. coli isoleucyl-tRNA synthetase alters zinc binding and aminoacylation activity. Biochemical and biophysical research communications, 216 2, 648-54

Jones, C M; Reyes, C J; Cook, R G; Krudy, G A; Rosevear, P R 1994. Synthetic macrophage activating peptides derived from the N-terminus of human MCF. Biochemical and biophysical research communications, 199 1, 20-5

Krudy, G A; Kleerekoper, Q; Guo, X; Howarth, J W; Solaro, R J; Rosevear, P R 1994. NMR studies delineating spatial relationships within the cardiac troponin I-troponin C complex. The Journal of biological chemistry, 269 38, 23731-5

Lin, X; Krudy, G A; Howarth, J; Brito, R M; Rosevear, P R; Putkey, J A 1994. Assignment and calcium dependence of methionyl epsilon C and epsilon H resonances in cardiac troponin C. Biochemistry, 33 48, 14434-42

Xu, B; Trawick, B; Krudy, G A; Phillips, R M; Zhou, L; Rosevear, P R 1994. Probing the metal binding sites of Escherichia coli isoleucyl-tRNA synthetase. Biochemistry, 33 2, 398-402

Brito, R M; Krudy, G A; Negele, J C; Putkey, J A; Rosevear, P R 1993. Calcium plays distinctive structural roles in the N- and C-terminal domains of cardiac troponin C. The Journal of biological chemistry, 268 28, 20966-73

Xu, B; Krudy, G A; Rosevear, P R 1993. Identification of the metal ligands and characterization of a putative zinc finger in methionyl-tRNA synthetase. The Journal of biological chemistry, 268 22, 16259-64

Krudy, G A; Brito, R M; Putkey, J A; Rosevear, P R 1992. Conformational changes in the metal-binding sites of cardiac troponin C induced by calcium binding. Biochemistry, 31 6, 1595-602

Brito, R M; Putkey, J A; Strynadka, N C; James, M N; Rosevear, P R 1991. Comparative NMR studies on cardiac troponin C and a mutant incapable of binding calcium at site II. Biochemistry, 30 42, 10236-45

Brito, R M; Rudolph, F B; Rosevear, P R 1991. Conformation of NADP+ bound to a type II dihydrofolate reductase. Biochemistry, 30 6, 1461-9

Williams, J S; Rosevear, P R 1991. A novel alpha-proton exchange reaction catalyzed by Escherichia coli methionyl-tRNA synthetase. Biochemistry, 30 26, 6412-6

Williams, J S; Rosevear, P R 1991. Nuclear overhauser effect studies of the conformations of Mg(alpha, beta-methylene)ATP bound to E. coli isoleucyl-tRNA synthetase. Biochemical and biophysical research communications, 176 2, 682-9

Williams, J S; Rosevear, P R 1991. Nuclear Overhauser effect studies on the conformations of Mg(alpha,beta-methylene)ATP bound to Escherichia coli methionyl-tRNA synthetase. The Journal of biological chemistry, 266 4, 2089-98

Brito, R M; Reddick, R; Bennett, G N; Rudolph, F B; Rosevear, P R 1990. Characterization and stereochemistry of cofactor oxidation by a type II dihydrofolate reductase. Biochemistry, 29 42, 9825-31

Flores-Carreón, A; Hixson, S H; Gómez, A; Shao, M C; Krudy, G; Rosevear, P R; Wold, F 1990. The processing of N-linked glycans in yeast. Mutually exclusive steps in the processing of a Man6 derivative by yeast membrane preparations. The Journal of biological chemistry, 265 2, 754-9

Sweeney, H L; Brito, R M; Rosevear, P R; Putkey, J A 1990. The low-affinity Ca2(+)-binding sites in cardiac/slow skeletal muscle troponin C perform distinct functions: site I alone cannot trigger contraction. Proceedings of the National Academy of Sciences of the United States of America, 87 24, 9538-42

Rosevear, P R; Mildvan, A S 1989. Ligand conformations and ligand-enzyme interactions as studied by the nuclear Overhauser effect. Methods in enzymology, 177 , 333-58

Shao, M C; Krudy, G; Rosevear, P R; Wold, F 1989. Protein matrix effects on glycan processing by mannosidase II and sialyl transferase from rat liver. Biochemistry, 28 9, 4077-83

Rosevear, P R 1988. Purification and NMR studies of [methyl-13C]methionine-labeled truncated methionyl-tRNA synthetase. Biochemistry, 27 20, 7931-9

Rosevear, P R; Fox, T L; Mildvan, A S 1987. Nuclear Overhauser effect studies of the conformations of MgATP bound to the active and secondary sites of muscle pyruvate kinase. Biochemistry, 26 12, 3487-93

Rosevear, P R; Powers, V M; Dowhan, D; Mildvan, A S; Kenyon, G L 1987. Nuclear overhauser effect studies on the conformation of magnesium adenosine 5'-triphosphate bound to rabbit muscle creatine kinase. Biochemistry, 26 17, 5338-44

Mildvan, A S; Rosevear, P R; Fry, D C; Bramson, H N; Kaiser, E T 1985. NMR studies of the mechanism of action and regulation of protein kinase. Current topics in cellular regulation, 27 , 133-44

Mildvan, A S; Kaiser, E T; Rosevear, P R; Bramson, H N 1984. NMR studies of the mechanism of cyclic AMP-dependent protein kinase. Federation proceedings, 43 11, 2634-9

Rosevear, P R; Fry, D C; Mildvan, A S; Doughty, M; O'Brian, C; Kaiser, E T 1984. NMR studies of the backbone protons and secondary structure of pentapeptide and heptapeptide substrates bound to bovine heart protein kinase. Biochemistry, 23 14, 3161-73

Rosevear, P R; Sellin, S; Mannervik, B; Kuntz, I D; Mildvan, A S 1984. NMR and computer modeling studies of the conformations of glutathione derivatives at the active site of glyoxalase I. The Journal of biological chemistry, 259 18, 11436-47

Mildvan, A S; Rosevear, P R; Granot, J; O 1983. Use of NMR and EPR to study cAMP-dependent protein kinase. Methods in enzymology, 99 , 93-119

Roff, C F; Rosevear, P R; Wang, J L; Barker, R 1983. Identification of carbohydrate-binding proteins from mouse and human fibroblasts. The Biochemical journal, 211 3, 625-9

Rosevear, P R; Bramson, H N; O'Brian, C; Kaiser, E T; Mildvan, A S 1983. Nuclear Overhauser effect studies of the conformations of tetraamminecobalt(III)-adenosine 5'-triphosphate free and bound to bovine heart protein kinase. Biochemistry, 22 14, 3439-47

Rosevear, P R; Chari, R V; Kozarich, J W; Sellin, S; Mannervik, B; Mildvan, A S 1983. 13C NMR studies of the product complex of glyoxalase I. The Journal of biological chemistry, 258 11, 6823-6

Barker, R; Nunez, H A; Rosevear, P; Serianni, A S 1982. 13C NMR analysis of complex carbohydrates. Methods in enzymology, 83 , 58-69

Rosevear, P R; Nunez, H A; Barker, R 1982. Synthesis and solution conformation of the type 2 blood group oligosaccharide alpha LFuc(1 leads to 2) beta DGal(1 leads to 4) beta DGlcNAc. Biochemistry, 21 6, 1421-31

Sellin, S; Rosevear, P R; Mannervik, B; Mildvan, A S 1982. Nuclear relaxation studies of the role of the essential metal in glyoxalase I. The Journal of biological chemistry, 257 17, 10023-9

Rosevear, P R; Desmeules, P; Kenyon, G L; Mildvan, A S 1981. Nuclear magnetic resonance studies of the role of histidine residues at the active site of rabbit muscle creatine kinase. Biochemistry, 20 21, 6155-64

Rosevear, P; VanAken, T; Baxter, J; Ferguson-Miller, S 1980. Alkyl glycoside detergents: a simpler synthesis and their effects on kinetic and physical properties of cytochrome c oxidase. Biochemistry, 19 17, 4108-15