Abstract

The four inter-related programs of this grant are proposed by a closely knit group of University of California investigators, with a common interest in the structure function relations of membrane bound enzymes, in electron transport processes, and in the mechanism of action of enzyme inhibitors and toxic substances. The enzymes being investigated include succinate dehydrogenase, fumarate reductase, monoamine oxidases A and B, NADH dehydrogenase, p-cresol methylhydroxylase, nitrate reductase, and copper protein with a role in bacterial electron transport. Numerous aspects of these enzymes will be explored, such as structure by crystallographic techniques, function of Fe-S clusters and the binding sites of covalently and non-covalently bound flavins by mutagenesis. Major efforts will be directed to further the exploration of the carnitine acyltransferases in mitochondria and peroxisomes and to further elucidate the sequence of events which lead from the entry of neurotoxic tetrahydropyridines into the circulation to nigrostriatal cell death.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL016251-19
Application #
3097553
Study Section
Heart, Lung, and Blood Research Review Committee A (HLBA)
Project Start
1978-09-01
Project End
1994-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
19
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Cecchini, Gary; Schroder, Imke; Gunsalus, Robert P et al. (2002) Succinate dehydrogenase and fumarate reductase from Escherichia coli. Biochim Biophys Acta 1553:140-57
Tornroth, Susanna; Yankovskaya, Victoria; Cecchini, Gary et al. (2002) Purification, crystallisation and preliminary crystallographic studies of succinate:ubiquinone oxidoreductase from Escherichia coli. Biochim Biophys Acta 1553:171-6
Ackrell, Brian A C (2002) Cytopathies involving mitochondrial complex II. Mol Aspects Med 23:369-84
Leger, C; Heffron, K; Pershad, H R et al. (2001) Enzyme electrokinetics: energetics of succinate oxidation by fumarate reductase and succinate dehydrogenase. Biochemistry 40:11234-45
Sablin, S O; Ramsay, R R (2001) Substrates but not inhibitors alter the redox potentials of monoamine oxidases. Antioxid Redox Signal 3:723-9
Maklashina, E; Rothery, R A; Weiner, J H et al. (2001) Retention of heme in axial ligand mutants of succinate-ubiquinone xxidoreductase (complex II) from Escherichia coli. J Biol Chem 276:18968-76
Chiu, H J; Johnson, E; Schroder, I et al. (2001) Crystal structures of a novel ferric reductase from the hyperthermophilic archaeon Archaeoglobus fulgidus and its complex with NADP+. Structure 9:311-9
Efimov, I; Cronin, C N; McIntire, W S (2001) Effects of noncovalent and covalent FAD binding on the redox and catalytic properties of p-cresol methylhydroxylase. Biochemistry 40:2155-66
Iverson, T M; Luna-Chavez, C; Schroder, I et al. (2000) Analyzing your complexes: structure of the quinol-fumarate reductase respiratory complex. Curr Opin Struct Biol 10:448-55
Luna-Chavez, C; Iverson, T M; Rees, D C et al. (2000) Overexpression, purification, and crystallization of the membrane-bound fumarate reductase from Escherichia coli. Protein Expr Purif 19:188-96

Showing the most recent 10 out of 164 publications