Nicotinate-nucleotide—dimethylbenzimidazole phosphoribosyltransferase

Phosphoribosyltransferase
crystal structure of cobt from thermus thermophilus hb8
Identifiers
Symbol	DBI_PRT
Pfam	PF02277
InterPro	IPR003200
SCOP2	1d0s / SCOPe / SUPFAM
CDD	cd02439
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure 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 ${\displaystyle \rightleftharpoons }$ 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.

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]

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]

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.

• Friedmann HC (1965). "Partial Purification and Properties of a Single Displacement Trans-N-Glycosidase". J. Biol. Chem. 240: 413–8. doi:10.1016/S0021-9258(18)97664-7. PMID 14253445.
• Friedmann HC, Fyfe JA (1969). "Pseudovitamin B 12 biosynthesis. Enzymatic formation of a new adenylic acid, 7-alpha-D-ribofuranosyladenine 5'-phosphate". J. Biol. Chem. 244 (7): 1667–71. doi:10.1016/S0021-9258(18)91736-9. PMID 5780835.
• Fyfe JA, Friedmann HC (1969). "Vitamin B 12 biosynthesis. Enzyme studies on the formation of the alpha-glycosidic nucleotide precursor". J. Biol. Chem. 244 (7): 1659–66. doi:10.1016/S0021-9258(18)91735-7. PMID 4238408.
• Cauchois L, Thibaut D, Debussche L, Crouzet J (1991). "Genetic analysis, nucleotide sequence, and products of two Pseudomonas denitrificans cob genes encoding nicotinate-nucleotide: dimethylbenzimidazole phosphoribosyltransferase and cobalamin (5'-phosphate) synthase". J. Bacteriol. 173 (19): 6066–73. doi:10.1128/jb.173.19.6066-6073.1991. PMC 208353. PMID 1917841.
• Cheong CG, Escalante-Semerena JC, Rayment I (2001). "Structural investigation of the biosynthesis of alternative lower ligands for cobamides by nicotinate mononucleotide: 5,6-dimethylbenzimidazole phosphoribosyltransferase from Salmonella enterica". J. Biol. Chem. 276 (40): 37612–20. doi:10.1074/jbc.M105390200. PMID 11441022.
• Cheong CG, Escalante-Semerena JC, Rayment I (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.