研究领域
Biochemistry
Structural Biology
We study how proteins work via conformational changes, posttranslational modifications, and protein:protein interactions.Our research areas include proteins in the nitric oxide-sGC-cGMP pathway crucial to the cardiovascular system, nitrogen oxides modifications, non canonical protein:RNA interactions, ligand:protein interactions and novel methods to detect protein:protein interactions. Our expertise, including molecular biology, biochemistry and spectroscopy, x-ray crystallography, and small-angle x-ray scattering allows us to answer key questions regarding enzyme catalysis, inhibition, recognition, and structural plasticity. We have a strong commitment to the training of graduate, undergraduate and now high-school students.
近期论文
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White MR, Khan MM, Deredge D, Ross CR, Quintyn R, Zucconi BE, Wysocki VH, Wintrode PL, Wilson GM, Garcin ED. "A Dimer Interface Mutation in Glyceraldehyde 3-Phosphate Dehydrogenase Regulates its Binding to AU-rich RNA" The Journal of Biological Chemistry, Journal of Biological Chemistry 290(3), (2015), 1770-1785, doi: 10.1074/jbc.M114.618165
Seeger F, Quintyn R, Tanimoto A, Williams GJ, Tainer JA, Wysocki VH, and Garcin ED. " Interfacial residues promote an optimal alignment of the catalytic center in human soluble guanylate cyclase: heterodimerization is required but not sufficient for activity" Biochemistry 53(13), (2014), 2153-2165. [ePub March 26 2014]. PMC3985721
Rogers NM, Seeger F, Garcin ED, Roberts DD, Isenberg JS. "Regulation of soluble guanylate cyclase by matricellular thrombospondins: implications for blood flow" Front. Physiol. 2014 Apr 4;5:134. eCollection 2014.
Purohit R, Fritz BG, The J, Issaian A, Weichsel A, David CL, Campbell E, Hausrath AC, Rassouli-Taylor L, Garcin ED, Gage MJ, Montfort WR. “YC-1 binding to the beta subunit of soluble guanylate cyclase overcomes allosteric inhibition by the alpha subunit” Biochemistry 53(1), (2014), 101-114. PMC3914721
Guan ZW, Haque MM, Wei CC, Garcin ED, Getzoff ED, Stuehr DJ “Lys842 in neuronal nitric-oxide synthase enables the autoinhibitory insert to antagonize calmodulin binding, increase FMN shielding, and suppress interflavin electron transfer” J. Biol. Chem. 285 (5), (2010), 3064-3075. PMC2823414
Elsa Garcin “La clé vers de nouveaux inhibiteurs de iNOS (A novel strategy to design iNOS specific inhibitors)” Médecines Sciences 25 (2009), 562-564.
Garcin ED, Arvai AS, Rosenfeld RK, Kroeger MD, Crane BR, Andersson G, Andrews G, Hamley PJ, Mallinder PR, Nicholls DJ, St-Gallay SA, Tinker AC, Gensmantel NP, Mete A, Cheshire DR, Connolly S, Stuehr DJ, Åberg A, Wallace AV, Tainer JA, Getzoff ED “Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase” Nat. Chem. Biol. 4 (2008), 700-707. PMC2868503
Garcin ED, Hosfield DJ, Haas BJ, Björas M, Cunningham R, Tainer JA “DNA apurinic/apyrimidinic site binding and excision by endonuclease IV” Nat. Struct. Mol. Biol. 15 (5), (2008), 515-522, doi:10.1038/nsmb.1414
Rameau GA, Tukey DS, Garcin-Hosfield ED, Misra C, Titcombe RF, Khatri L, Getzoff ED, Ziff EB “Biphasic coupling of neuronal nitric oxide synthase phosphorylation to the NMDA receptor induces AMPA receptor trafficking and neuronal cell death” J. Neurosciences 27 (13), (2007), 3445-3455. PMID: 17392461
Panda K, Haque MM, Garcin-Hosfield ED, Durra D, Getzoff ED, Stuehr DJ “Surface charge interactions of electron transport modules govern catalysis by nitric oxide synthase” J. Biol. Chem. 281 (48), (2006), 36819-36827.
Tiso M, Konas DW, Panda K, Garcin ED, Sharma M, Getzoff ED, Stuehr DJ "C-terminal tail residue ARG1400 enables NADPH to regulate electron transfer in neuronal nitric oxide synthase" J. Biol. Chem. 280 (47), (2005), 39208-39219, doi:10.1074/jbc.M507775200
Volbeda A, Martin L, Cavazza C, Matho M, Faber BW, Roseboom W, Albracht SPJ, Garcin E, Rousset M, Fontecilla-Camps J-C "Structural differences between the ready and unready oxidized states of [NiFe] hydrogenases" J. Biol. Inorg. Chem. 10 (3), (2005), 239-249, PMID: 15803334
Garcin ED, Bruns CM, Lloyd SJ, Hosfield DJ, Tiso M, Gachhui R, Stuehr DJ, Tainer JA and Getzoff ED “Structural basis for isozyme-specific regulation of electron transfer in nitric oxide synthase" J. Biol. Chem. 279 (3), (2004), 37918-37927, doi:10.1074/jbc.M406204200
Rosenfeld RJ, Garcin ED, Panda K, Andersson G, Aberg A, Wallace AV, Morris GM, Olson AJ, Stuehr DJ, Tainer JA, Getzoff ED "Conformational Changes in Nitric Oxide Synthases Induced by Chlorzoxazone and Nitroindazoles: Crystallographic and Computational Analyses of Inhibitor Potency" Biochemistry, 41 (47), (2002), 13915-13925, doi:10.1021/bi026313j
Wei CC, Wang Z-Q, Durra D, Hemann C, Hille R, Garcin ED, Getzoff ED, Stuehr DJ "The three nitric-oxide synthases differ in their kinetics of tetrahydrobiopterin radical formation, heme-dioxy reduction, and arginine hydroxylation" J. Biol. Chem. 280 (10), (2005), 8929-8935, doi:10.1074/jbc.M409737200
Richard SB, Madern D, Garcin E, Zaccai G “Halophilic adaptation: Novel solvent protein interactions observed in the 2.9 and the 2.6 Angstrom resolution structures of the wild type and a mutant of Malate Dehydrogenase from Haloarcula Marismortui" Biochemistry, 39 (5), (2000), 992-1000, doi: 10.1021/bi991001a
E Garcin, X Vernede, C Hatchikian, A Volbeda, M Frey, J-C Fontecilla-Camps "The Crystal Structure of a reduced [NiFeSe] hydrogenase provides an image of the activated catalytic center" Structure, 7 (5), (1999), 557-566, doi:10.1016/S0969-2126(99)80072-0
Garcin E, Montet Y, Volbeda A, Hatchikian E.C, Frey M, Fontecilla-Camps J-C "Structural Bases for the catalytic mechanism of [NiFe] hydrogenases", Biochem. Soc. Trans., 26 (3), (1998), 396-401, PMID: 9765886
Y Montet, E Garcin, A Volbeda, C Hatchikian, M. Frey, J-C Fontecilla-Camps "Structural bases for the catalytic mechanism of NiFe hydrogenase" Pure & Appl. Chem., 70 (1), (1998), 25-31.
J-C Fontecilla-Camps, M Frey, E Garcin, C Hatchikian, Y Montet, C Piras, X Vernede, A Volbeda "Hydrogenase: a hydrogen-metabolizing enzyme. What do the crystal structures tell us about its mode of action?" Biochimie, 79 (1997), 661-666.
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