DTDP-glucose 4,6-dehydratase

dTDP-glucose 4,6-dehydratase
Identifiers
EC number 4.2.1.46
CAS number 37259-54-4
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

In enzymology, a dTDP-glucose 4,6-dehydratase (EC 4.2.1.46) is an enzyme that catalyzes the chemical reaction

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

Hence, this enzyme has one substrate, dTDP-glucose, and two products, dTDP-4-dehydro-6-deoxy-D-glucose and 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 Rossman 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, 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.
  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. 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

  • Gilbert JM, Matshushi M, Strominger JL (1965). "Thymidine diphosphate 4-acetamido-4,6-dideoxyhexoses. II Purification and properties of thymidine diphosphate d-glucose oxidoreductase". J. Biol. Chem. 240: 1305–8. PMID 14284740. 
  • Melo A, Elliott WH, Glaser L (1968). "The mechanism of 6-deoxyhexose synthesis. I. Intramolecular hydrogen transfer catalyzed by deoxythymidine diphosphate D-glucose oxidoreductase". J. Biol. Chem. 243 (7): 1467–74. PMID 4869560. 
  • Wang SF, Gabriel O (1969). "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. PMID 4307450. 
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