Biology:dTDP-glucose 4,6-dehydratase

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dTDP-glucose 4,6-dehydratase
Identifiers
EC number4.2.1.46
CAS number37259-54-4
Alt. namesRmlB
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

The enzyme dTDP-glucose 4,6-dehydratase (EC 4.2.1.46) catalyzes the chemical reaction

dTDP-glucose [math]\displaystyle{ \rightleftharpoons }[/math] 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.

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 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. ↑ "Concerted and stepwise dehydration mechanisms observed in wild-type and mutated Escherichia coli dTDP-glucose 4,6-dehydratase". Biochemistry 41 (8): 2797–804. February 2002. doi:10.1021/bi011748c. PMID 11851427. 
  4. ↑ "Mechanistic roles of Thr134, Tyr160, and Lys 164 in the reaction catalyzed by dTDP-glucose 4,6-dehydratase". Biochemistry 40 (31): 9187–95. August 2001. doi:10.1021/bi0108249. PMID 11478886. 
  5. ↑ Allard, STM; Beis K; Giraud MF; Hegeman AD; Gross JW; Wilmouth RC; Whitfield C; Graninger M et al. (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

  • "Thymidine diphosphate 4-acetamido-4,6-dideoxyhexoses. II Purification and properties of thymidine diphosphate d-glucose oxidoreductase". J. Biol. Chem. 240: 1305–8. 1965. PMID 14284740. 
  • "The mechanism of 6-deoxyhexose synthesis. I. Intramolecular hydrogen transfer catalyzed by deoxythymidine diphosphate D-glucose oxidoreductase". J. Biol. Chem. 243 (7): 1467–74. 1968. PMID 4869560. 
  • "Biological mechanisms involved in the formation of deoxy sugars. V Isolation and crystallization of thymidine diphosphate-D-glucose oxidoreductase from Escherichia coli B". J. Biol. Chem. 244 (13): 3430–7. 1969. PMID 4307450. 




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