Nicotinate-nucleotide—dimethylbenzimidazole phosphoribosyltransferase explained

nicotinate-nucleotide-dimethylbenzimidazole phosphoribosyltransferase
Ec Number:	2.4.2.21
Cas Number:	37277-76-2
Go Code:	0008939

Symbol:	DBI_PRT
Phosphoribosyltransferase
Pfam:	PF02277
Interpro:	IPR003200
Scop:	1d0s
Cdd:	cd02439

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

beta-nicotinate D-ribonucleotide + 5,6-dimethylbenzimidazole

\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.

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

See main article: Cobalamin biosynthesis. 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,,,,,,,,,,,,,,,,,,,,,,,,,,, and .

Further reading

• Friedmann HC . 1965 . Partial Purification and Properties of a Single Displacement Trans-N-Glycosidase . J. Biol. Chem. . 240 . 413 - 8 . 10.1016/S0021-9258(18)97664-7 . 14253445 . free .
• 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 . 1667 - 71 . 5780835 . 7 . 10.1016/S0021-9258(18)91736-9 . free .
• Fyfe JA, Friedmann HC . 1969 . Vitamin B 12 biosynthesis. Enzyme studies on the formation of the alpha-glycosidic nucleotide precursor . J. Biol. Chem. . 244 . 1659 - 66 . 4238408 . 7 . 10.1016/S0021-9258(18)91735-7 . free .
• 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 . 6066 - 73 . 1917841 . 19 . 208353 . 10.1128/jb.173.19.6066-6073.1991 .
• 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 . 37612 - 20 . 11441022 . 10.1074/jbc.M105390200 . 40 . free .
• 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 . 41120 - 7 . 12101181 . 10.1074/jbc.M203535200 . 43 . free .

Notes and References

1. Trzebiatowski JR, O'Toole GA, Escalante-Semerena JC . 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 . June 1994 . 8206834 . 205545 . 10.1128/jb.176.12.3568-3575.1994.
2. Cheong CG, Escalante-Semerena JC, Rayment I . 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 . October 2002 . 12101181 . 10.1074/jbc.M203535200 . free .
3. Lawrence JG, Roth JR . The cobalamin (coenzyme B12) biosynthetic genes of Escherichia coli . J. Bacteriol. . 177 . 22 . 6371–80 . November 1995 . 7592411 . 177486 . 10.1128/jb.177.22.6371-6380.1995.
4. Raux E, Lanois A, Levillayer F, Warren MJ, Brody E, Rambach A, Thermes C . Salmonella typhimurium cobalamin (vitamin B12) biosynthetic genes: functional studies in S. typhimurium and Escherichia coli . J. Bacteriol. . 178 . 3 . 753–67 . February 1996 . 8550510 . 177722 . 10.1128/jb.178.3.753-767.1996.
5. Scott AI, Roessner CA . Biosynthesis of cobalamin (vitamin B(12)) . Biochem. Soc. Trans. . 30 . 4 . 613–20 . August 2002 . 12196148 . 10.1042/bst0300613.
6. Book: Roessner CA, Santander PJ, Scott AI . Cofactor Biosynthesis . Multiple biosynthetic pathways for vitamin B12: variations on a central theme . Vitam. Horm. . 61 . 267–97 . 2001 . 11153269 . 10.1016/s0083-6729(01)61009-4. Vitamins & Hormones . 9780127098616 .