EC 2.7.7.62 - Adenosylcobinamide-phosphate guanylyltransferase

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IntEnz Enzyme Nomenclature
EC 2.7.7.62

Names

Accepted name:
adenosylcobinamide-phosphate guanylyltransferase
Other names:
AdoCbi kinase/AdoCbi-phosphate guanylyltransferase
CobU
adenosylcobinamide kinase/adenosylcobinamide-phosphate guanylyltransferase
Systematic name:
GTP:adenosylcobinamide-phosphate guanylyltransferase

Reaction

Comments:

In Salmonella typhimurium LT2, under anaerobic conditions, CobU (EC 2.7.7.62 and EC 2.7.1.156), CobT (EC 2.4.2.21), CobC (EC 3.1.3.73) and CobS (EC 2.7.8.26) catalyse reactions in the nucleotide loop assembly pathway, which convert adenosylcobinamide (AdoCbi) into adenosylcobalamin (AdoCbl). CobT and CobC are involved in 5,6-dimethylbenzimidazole activation whereby 5,6-dimethylbenzimidazole is converted into its riboside, α-ribazole. The second branch of the nuclotide loop assembly pathway is the cobinamide (Cbi) activation branch where AdoCbi or adenosylcobinamide-phosphate is converted into the activated intermediate AdoCbi-GDP by the bifunctional enzyme Cob U. The final step in adenosylcobalamin biosynthesis is the condensation of AdoCbi-GDP with α-ribazole, which is catalysed by EC 2.7.8.26, cobalamin synthase (CobS), to yield adenosylcobalamin. CobU is a bifunctional enzyme that has both kinase (EC 2.7.1.156) and guanylyltransferase (EC 2.7.7.62) activities. However, both activities are not required at all times. The kinase activity has been proposed to function only when S. typhimurium is assimilating cobinamide whereas the guanylyltransferase activity is required for both assimilation of exogenous cobinamide and for de novo synthesis of adenosylcobalamin [4]. The guanylyltransferase reaction is a two-stage reaction with formation of a CobU-GMP intermediate [1]. Guanylylation takes place at histidine-46.

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , DIAGRAM , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Structural data: CSA , EC2PDB
Gene Ontology: GO:0008820
UniProtKB/Swiss-Prot:

References

  1. O'Toole, G.A. and Escalante-Semerena, J.C.
    Purification and characterization of the bifunctional CobU enzyme of Salmonella typhimurium LT2. Evidence for a CobU-GMP intermediate.
    J. Biol. Chem. 270: 23560-23569 (1995). [PMID: 7559521]
  2. Thompson, T.B., Thomas, M.G., Escalante-Semerena, J.C. and Rayment, I.
    Three-dimensional structure of adenosylcobinamide kinase/adenosylcobinamide phosphate guanylyltransferase from Salmonella typhimurium determined to 2.3 Å resolution.
    Biochemistry 37: 7686-7695 (1998). [PMID: 9601028]
  3. Thompson, T.B., Thomas, M.G., Escalante-Semerena, J.C. and Rayment, I.
    Three-dimensional structure of adenosylcobinamide kinase/adenosylcobinamide phosphate guanylyltransferase (CobU) complexed with GMP: evidence for a substrate-induced transferase active site.
    Biochemistry 38: 12995-13005 (1999). [PMID: 10529169]
  4. Thomas, M.G., Thompson, T.B., Rayment, I. and Escalante-Semerena, J.C.
    Analysis of the adenosylcobinamide kinase/adenosylcobinamide-phosphate guanylyltransferase (CobU) enzyme of Salmonella typhimurium LT2. Identification of residue His-46 as the site of guanylylation.
    J. Biol. Chem. 275: 27576-27586 (2000). [PMID: 10869342]
  5. Warren, M.J., Raux, E., Schubert, H.L. and Escalante-Semerena, J.C.
    The biosynthesis of adenosylcobalamin (vitamin B12).
    Nat. Prod. Rep. 19: 390-412 (2002). [PMID: 12195810]

[EC 2.7.7.62 created 2004]