nicotinate-nucleotide-dimethylbenzimidazole phosphoribosyltransferase
Identifiers
EC no.2.4.2.21
CAS no.37277-76-2
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins
Phosphoribosyltransferase
crystal structure of cobt from thermus thermophilus hb8
Identifiers
SymbolDBI_PRT
PfamPF02277
InterProIPR003200
SCOP21d0s / SCOPe / SUPFAM
CDDcd02439
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

In enzymology, a nicotinate-nucleotide-dimethylbenzimidazole phosphoribosyltransferase (EC 2.4.2.21) is an enzyme that catalyzes the chemical reaction

beta-nicotinate D-ribonucleotide + 5,6-dimethylbenzimidazole nicotinate + alpha-ribazole 5'-phosphate

Thus, the two substrates of this enzyme are beta-nicotinate D-ribonucleotide and 5,6-dimethylbenzimidazole, whereas its two products are nicotinate and alpha-ribazole 5'-phosphate.

This enzyme belongs to the family of glycosyltransferases, specifically the pentosyltransferases. The systematic name of this enzyme class is nicotinate-nucleotide:5,6-dimethylbenzimidazole phospho-D-ribosyltransferase. Other names in common use include CobT, nicotinate mononucleotide-dimethylbenzimidazole phosphoribosyltransferase, nicotinate ribonucleotide:benzimidazole (adenine) phosphoribosyltransferase, nicotinate-nucleotide:dimethylbenzimidazole phospho-D-ribosyltransferase, and nicotinate mononucleotide (NaMN):5,6-dimethylbenzimidazole phosphoribosyltransferase. This enzyme is part of the biosynthetic pathway to cobalamin (vitamin B12) in bacteria.

Function

This enzyme plays a central role in the synthesis of alpha-ribazole-5'-phosphate, an intermediate for the lower ligand of cobalamin.[1] It is one of the enzymes of the anaerobic pathway of cobalamin biosynthesis, and one of the four proteins (CobU, CobT, CobC, and CobS) involved in the synthesis of the lower ligand and the assembly of the nucleotide loop.[2][3]

Biosynthesis of cobalamin

Vitamin B12 (cobalamin) is used as a cofactor in a number of enzyme-catalysed reactions in bacteria, archaea and eukaryotes.[4] The biosynthetic pathway to adenosylcobalamin from its five-carbon precursor, 5-aminolaevulinic acid, can be divided into three sections: (1) the biosynthesis of uroporphyrinogen III from 5-aminolaevulinic acid; (2) the conversion of uroporphyrinogen III into the ring-contracted, deacylated intermediate precorrin 6 or cobalt-precorrin 6; and (3) the transformation of this intermediate to form adenosylcobalamin.[5] Cobalamin is synthesised by bacteria and archaea via two alternative routes that differ primarily in the steps of section 2 that lead to the contraction of the macrocycle and excision of the extruded carbon molecule (and its attached methyl group).[6] One pathway (exemplified by Pseudomonas denitrificans) incorporates molecular oxygen into the macrocycle as a prerequisite to ring contraction, and has consequently been termed the aerobic pathway. The alternative, anaerobic, route (exemplified by Salmonella typhimurium) takes advantage of a chelated cobalt ion, in the absence of oxygen, to set the stage for ring contraction.[5]

Structural studies

As of late 2007, 28 structures have been solved for this class of enzymes, with PDB accession codes 1D0S, 1D0V, 1JH8, 1JHA, 1JHM, 1JHP, 1JHQ, 1JHR, 1JHU, 1JHV, 1JHX, 1JHY, 1L4B, 1L4E, 1L4F, 1L4G, 1L4H, 1L4K, 1L4L, 1L4M, 1L4N, 1L5F, 1L5K, 1L5L, 1L5M, 1L5N, 1L5O, and 1WX1.

References

  1. ↑ Trzebiatowski JR, O'Toole GA, Escalante-Semerena JC (June 1994). "The cobT gene of Salmonella typhimurium encodes the NaMN: 5,6-dimethylbenzimidazole phosphoribosyltransferase responsible for the synthesis of N1-(5-phospho-alpha-D-ribosyl)-5,6-dimethylbenzimidazole, an intermediate in the synthesis of the nucleotide loop of cobalamin". J. Bacteriol. 176 (12): 3568–75. doi:10.1128/jb.176.12.3568-3575.1994. PMC 205545. PMID 8206834.
  2. ↑ Cheong CG, Escalante-Semerena JC, Rayment I (October 2002). "Capture of a labile substrate by expulsion of water molecules from the active site of nicotinate mononucleotide:5,6-dimethylbenzimidazole phosphoribosyltransferase (CobT) from Salmonella enterica". J. Biol. Chem. 277 (43): 41120–7. doi:10.1074/jbc.M203535200. PMID 12101181.
  3. ↑ Lawrence JG, Roth JR (November 1995). "The cobalamin (coenzyme B12) biosynthetic genes of Escherichia coli". J. Bacteriol. 177 (22): 6371–80. doi:10.1128/jb.177.22.6371-6380.1995. PMC 177486. PMID 7592411.
  4. ↑ Raux E, Lanois A, Levillayer F, Warren MJ, Brody E, Rambach A, Thermes C (February 1996). "Salmonella typhimurium cobalamin (vitamin B12) biosynthetic genes: functional studies in S. typhimurium and Escherichia coli". J. Bacteriol. 178 (3): 753–67. doi:10.1128/jb.178.3.753-767.1996. PMC 177722. PMID 8550510.
  5. 1 2 Scott AI, Roessner CA (August 2002). "Biosynthesis of cobalamin (vitamin B(12))". Biochem. Soc. Trans. 30 (4): 613–20. doi:10.1042/bst0300613. PMID 12196148.
  6. ↑ Roessner CA, Santander PJ, Scott AI (2001). "Multiple biosynthetic pathways for vitamin B12: variations on a central theme". Cofactor Biosynthesis. Vitamins & Hormones. Vol. 61. pp. 267–97. doi:10.1016/s0083-6729(01)61009-4. ISBN 9780127098616. PMID 11153269. {{cite book}}: |journal= ignored (help)

Further reading

This article incorporates text from the public domain Pfam and InterPro: IPR003200
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