DTDP-glucose 4,6-dehydratase

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dTDP-glucose 4,6-dehydratase
Identifiers
EC no. 4.2.1.46
CAS no. 37259-54-4
Alt. names RmlB
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MetaCyc metabolic pathway
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The enzyme dTDP-glucose 4,6-dehydratase (EC 4.2.1.46) catalyzes the chemical reaction

Contents

dTDP-glucose dTDP-4-dehydro-6-deoxy-D-glucose + H2O

Structure and mechanism of action

The first protein structures of a dTDP-glucose 4,6-dehydratase (RmlB) were completed by Jim Thoden in the Hazel Holden lab (University of Wisconsin–Madison) and Simon Allard in the Jim Naismith lab (University of St Andrews). [1] [2] Further structural, mutagenic, and enzymatic studies by both groups, along with important mechanistic work by the W. Wallace Cleland and Perry Frey groups have led to a good understanding of this enzyme. [3] [4] In brief summary, the enzyme is a dimeric protein with a Rossmann fold; it uses the tightly bound coenzyme NAD + for transiently oxidizing the substrate, activating it for the dehydration step. [5] [6]

Nomenclature

This enzyme belongs to the family of lyases, specifically the hydro-lyases, which cleave carbon-oxygen bonds. The systematic name of this enzyme class is dTDP-glucose 4,6-hydro-lyase (dTDP-4-dehydro-6-deoxy-D-glucose-forming). Other names in common use include thymidine diphosphoglucose oxidoreductase, TDP-glucose oxidoreductase, RmlB , DESIV, and dTDP-glucose 4,6-hydro-lyase. This enzyme participates in 4 metabolic pathways: nucleotide sugars metabolism, streptomycin biosynthesis, polyketide sugar unit biosynthesis, and biosynthesis of vancomycin group antibiotics.

Related Research Articles

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<span class="mw-page-title-main">GDP-mannose 4,6-dehydratase</span>

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<span class="mw-page-title-main">Starch synthase</span> Enzyme family

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<span class="mw-page-title-main">Glucose-1-phosphate adenylyltransferase</span>

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<span class="mw-page-title-main">Thymidylate kinase</span>

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DTDP-6-deoxy-L-talose 4-dehydrogenase (NAD+) (EC 1.1.1.339, tll (gene name)) is an enzyme with systematic name dTDP-6-deoxy-beta-L-talose:NAD+ 4-oxidoreductase. This enzyme catalyses the following chemical reaction

References

  1. Allard, STM; Cleland WW; Holden, HM. (2004). "High resolution X-ray structure of dTDP-glucose 4,6-dehydratase from Streptomyces venezuelae". Journal of Biological Chemistry. 279 (3): 2211–20. doi: 10.1074/jbc.M310134200 . PMID   14570895.
  2. Allard, STM; Giraud, M-F; Naismith, JH; et al. (2001). "The crystal structure of dTDP-d-glucose 4,6-dehydratase (RmlB) from Salmonella enterica serovar typhimurium, the second enzyme in the dTDP-l-rhamnose pathway". Journal of Molecular Biology. 307 (1): 283–295. doi:10.1006/jmbi.2000.4470. PMID   11243820.
  3. Hegeman AD, Gross JW, Frey PA (February 2002). "Concerted and stepwise dehydration mechanisms observed in wild-type and mutated Escherichia coli dTDP-glucose 4,6-dehydratase". Biochemistry. 41 (8): 2797–804. CiteSeerX   10.1.1.557.8752 . doi:10.1021/bi011748c. PMID   11851427.
  4. Gerratana B, Cleland WW, Frey PA (August 2001). "Mechanistic roles of Thr134, Tyr160, and Lys 164 in the reaction catalyzed by dTDP-glucose 4,6-dehydratase". Biochemistry. 40 (31): 9187–95. doi:10.1021/bi0108249. PMID   11478886.
  5. Allard, STM; Beis K; Giraud MF; Hegeman AD; Gross JW; Wilmouth RC; Whitfield C; Graninger M; Messner P; Allen AG; Maskell DJ; Naismith JH (January 2002). "Toward a structural understanding of the dehydratase mechanism". Structure. 10 (1): 81–92. doi: 10.1016/S0969-2126(01)00694-3 . PMID   11796113.
  6. Beis K, Allard; STM, Hegeman AD; Murshudov G; Philp D; Naismith JH (October 2003). "The structure of NADH in the enzyme dTDP-d-glucose dehydratase (RmlB)". J. Am. Chem. Soc. 125 (39): 11872–8. doi:10.1021/ja035796r. PMID   14505409.

Further reading