Abstract

Flavin coenzyme analogs, synthetically modified at various key ring loci, will be used to analyze and factor out elements of flavin redox function, such as two electron/one electron capacity, sites of entry and exit of electrons, and nature of O2 reductive activation and splitting. Experiments will focus on mechanistic studies of the bacterial HgII reductases, cyclohexanone monooxygenases, methanogen hydrogenase, the superoxide-generating system from human leukocytes, and an S-oxygenating flavoenzyme from liver.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM021643-12
Application #
3270614
Study Section
Biochemistry Study Section (BIO)
Project Start
1978-05-01
Project End
1988-04-30
Budget Start
1986-05-01
Budget End
1987-04-30
Support Year
12
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

Yeh, Ellen; Cole, Lindsay J; Barr, Eric W et al. (2006) Flavin redox chemistry precedes substrate chlorination during the reaction of the flavin-dependent halogenase RebH. Biochemistry 45:7904-12
Liu, Fei; Garneau, Sylvie; Walsh, Christopher T (2004) Hybrid nonribosomal peptide-polyketide interfaces in epothilone biosynthesis: minimal requirements at N and C termini of EpoB for elongation. Chem Biol 11:1533-42
Lessard, I A; Walsh, C T (1999) Mutational analysis of active-site residues of the enterococcal D-ala-D-Ala dipeptidase VanX and comparison with Escherichia coli D-ala-D-Ala ligase and D-ala-D-Ala carboxypeptidase VanY. Chem Biol 6:177-87
Lessard, I A; Walsh, C T (1999) VanX, a bacterial D-alanyl-D-alanine dipeptidase: resistance, immunity, or survival function? Proc Natl Acad Sci U S A 96:11028-32
Stoll, V S; Simpson, S J; Krauth-Siegel, R L et al. (1997) Glutathione reductase turned into trypanothione reductase: structural analysis of an engineered change in substrate specificity. Biochemistry 36:6437-47
Rennex, D; Cummings, R T; Pickett, M et al. (1993) Role of tyrosine residues in Hg(II) detoxification by mercuric reductase from Bacillus sp. strain RC607. Biochemistry 32:7475-8
Smith, K; Nadeau, K; Bradley, M et al. (1992) Purification of glutathionylspermidine and trypanothione synthetases from Crithidia fasciculata. Protein Sci 1:874-83
Moore, M J; Miller, S M; Walsh, C T (1992) C-terminal cysteines of Tn501 mercuric ion reductase. Biochemistry 31:1677-85
Leichus, B N; Bradley, M; Nadeau, K et al. (1992) Kinetic isotope effect analysis of the reaction catalyzed by Trypanosoma congolense trypanothione reductase. Biochemistry 31:6414-20
Walsh, C; Bradley, M; Nadeau, K (1992) Molecular studies on trypanothione reductase: an antiparasitic target enzyme. Curr Top Cell Regul 33:409-17

Showing the most recent 10 out of 26 publications