1ps9 Citations

The crystal structure and reaction mechanism of Escherichia coli 2,4-dienoyl-CoA reductase.

J. Biol. Chem. 278 37553-60 (2003)
Cited: 21 times
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Escherichia coli 2,4-dienoyl-CoA reductase is an iron-sulfur flavoenzyme required for the metabolism of unsaturated fatty acids with double bonds at even carbon positions. The enzyme contains FMN, FAD, and a 4Fe-4S cluster and exhibits sequence homology to another iron-sulfur flavoprotein, trimethylamine dehydrogenase. It also requires NADPH as an electron source, resulting in reduction of the C4-C5 double bond of the acyl chain of the CoA thioester substrate. The structure presented here of a ternary complex of E. coli 2,4-dienoyl-CoA reductase with NADP+ and a fatty acyl-CoA substrate reveals a possible mechanism for substrate reduction and provides details of a plausible electron transfer mechanism involving both flavins and the iron-sulfur cluster. The reaction is initiated by hydride transfer from NADPH to FAD, which in turn transfers electrons, one at a time, to FMN via the 4Fe-4S cluster. In the final stages of the reaction, the fully reduced FMN provides a hydride ion to the C5 atom of substrate, and Tyr-166 and His-252 are proposed to form a catalytic dyad that protonates the C4 atom of the substrate and complete the reaction. Inspection of the substrate binding pocket explains the relative promiscuity of the enzyme, catalyzing reduction of both 2-trans,4-cis- and 2-trans,4-trans-dienoyl-CoA thioesters.

Articles - 1ps9 mentioned but not cited (3)

  1. Evolution of function in the "two dinucleotide binding domains" flavoproteins. Ojha S, Meng EC, Babbitt PC. PLoS Comput. Biol. 3 e121 (2007)
  2. ResBoost: characterizing and predicting catalytic residues in enzymes. Alterovitz R, Arvey A, Sankararaman S, Dallett C, Freund Y, Sjölander K. BMC Bioinformatics 10 197 (2009)
  3. The combined structural and kinetic characterization of a bacterial nitronate monooxygenase from Pseudomonas aeruginosa PAO1 establishes NMO class I and II. Salvi F, Agniswamy J, Yuan H, Vercammen K, Pelicaen R, Cornelis P, Spain JC, Weber IT, Gadda G. J. Biol. Chem. 289 23764-23775 (2014)

Reviews citing this publication (1)

  1. Structural biology of the thioester-dependent degradation and synthesis of fatty acids. Bhaumik P, Koski MK, Glumoff T, Hiltunen JK, Wierenga RK. Curr. Opin. Struct. Biol. 15 621-628 (2005)

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  3. Clostridium scindens baiCD and baiH genes encode stereo-specific 7alpha/7beta-hydroxy-3-oxo-delta4-cholenoic acid oxidoreductases. Kang DJ, Ridlon JM, Moore DR, Barnes S, Hylemon PB. Biochim. Biophys. Acta 1781 16-25 (2008)
  4. Identification and expression of genes involved in the conversion of daidzein and genistein by the equol-forming bacterium Slackia isoflavoniconvertens. Schröder C, Matthies A, Engst W, Blaut M, Braune A. Appl. Environ. Microbiol. 79 3494-3502 (2013)
  5. Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas' disease treatment. Capriles PV, Guimarães AC, Otto TD, Miranda AB, Dardenne LE, Degrave WM. BMC Genomics 11 610 (2010)
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  13. Identification of proteins capable of metal reduction from the proteome of the Gram-positive bacterium Desulfotomaculum reducens MI-1 using an NADH-based activity assay. Otwell AE, Sherwood RW, Zhang S, Nelson OD, Li Z, Lin H, Callister SJ, Richardson RE. Environ. Microbiol. 17 1977-1990 (2015)
  14. Sequence Conservation, Radial Distance and Packing Density in Spherical Viral Capsids. Chang CM, Huang YW, Lee CW, Huang TT, Shih CS, Hwang JK. PLoS ONE 10 e0132234 (2015)
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  16. Molecular dissection of a putative iron reductase from Desulfotomaculum reducens MI-1. Li Z, Kim DD, Nelson OD, Otwell AE, Richardson RE, Callister SJ, Lin H. Biochem. Biophys. Res. Commun. 467 503-508 (2015)
  17. Alkene hydrogenation activity of enoate reductases for an environmentally benign biosynthesis of adipic acid. Joo JC, Khusnutdinova AN, Flick R, Kim T, Bornscheuer UT, Yakunin AF, Mahadevan R. Chem Sci 8 1406-1413 (2017)

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