dTDP-glucose 4,6-dehydratase
The enzyme dTDP-glucose 4,6-dehydratase (EC 4.2.1.46) catalyzes the chemical reaction
- dTDP-glucose dTDP-4-dehydro-6-deoxy-D-glucose + H2O
| dTDP-glucose 4,6-dehydratase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 4.2.1.46 | ||||||||
| CAS no. | 37259-54-4 | ||||||||
| Alt. names | RmlB | ||||||||
| 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 / QuickGO | ||||||||
| |||||||||
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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.