Binding of cob(II)alamin to the adenosylcobalamin-dependent ribonucleotide reductase from Lactobacillus leichmannii

Identification of dimethylbenzimidazole as the axial ligand

Christopher C. Lawrence, Gary J. Gerfen, Vicente Samano, Rainer Nitsche, Morris J. Robins, János Rétey, JoAnne Stubbe

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

The ribonucleoside triphosphate reductase (RTPR) from Lactobacillus leichmannii catalyzes the reduction of nucleoside 5'-triphosphates to 2'- deoxynucleoside 5'-triphosphates and uses coenzyme B12, adenosylcobalamin (AdoCbl), as a cofactor. Use of a mechanism-based inhibitor, 2'-deoxy-2'- methylenecytidine 5'-triphosphate, and isotopically labeled RTPR and AdoCbl in conjunction with EPR spectroscopy has allowed identification of the lower axial ligand of cob(II)alamin when bound to RTPR. In common with the AdoCbl- dependent enzymes catalyzing irreversible heteroatom migrations and in contrast to the enzymes catalyzing reversible carbon skeleton rearrangements, the dimethylbenzimidazole moiety of the cofactor is not displaced by a protein histidine upon binding to RTPR.

Original languageEnglish (US)
Pages (from-to)7039-7042
Number of pages4
JournalJournal of Biological Chemistry
Volume274
Issue number11
DOIs
StatePublished - Mar 12 1999

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ribonucleoside-triphosphate reductase
Lactobacillus leichmannii
Ribonucleotide Reductases
Ligands
Enzymes
Nucleosides
Histidine
Skeleton
Paramagnetic resonance
Spectrum Analysis
Carbon
Spectroscopy
cobamamide
cob(II)alamin

ASJC Scopus subject areas

  • Biochemistry

Cite this

Binding of cob(II)alamin to the adenosylcobalamin-dependent ribonucleotide reductase from Lactobacillus leichmannii : Identification of dimethylbenzimidazole as the axial ligand. / Lawrence, Christopher C.; Gerfen, Gary J.; Samano, Vicente; Nitsche, Rainer; Robins, Morris J.; Rétey, János; Stubbe, JoAnne.

In: Journal of Biological Chemistry, Vol. 274, No. 11, 12.03.1999, p. 7039-7042.

Research output: Contribution to journalArticle

Lawrence, Christopher C. ; Gerfen, Gary J. ; Samano, Vicente ; Nitsche, Rainer ; Robins, Morris J. ; Rétey, János ; Stubbe, JoAnne. / Binding of cob(II)alamin to the adenosylcobalamin-dependent ribonucleotide reductase from Lactobacillus leichmannii : Identification of dimethylbenzimidazole as the axial ligand. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 11. pp. 7039-7042.
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abstract = "The ribonucleoside triphosphate reductase (RTPR) from Lactobacillus leichmannii catalyzes the reduction of nucleoside 5'-triphosphates to 2'- deoxynucleoside 5'-triphosphates and uses coenzyme B12, adenosylcobalamin (AdoCbl), as a cofactor. Use of a mechanism-based inhibitor, 2'-deoxy-2'- methylenecytidine 5'-triphosphate, and isotopically labeled RTPR and AdoCbl in conjunction with EPR spectroscopy has allowed identification of the lower axial ligand of cob(II)alamin when bound to RTPR. In common with the AdoCbl- dependent enzymes catalyzing irreversible heteroatom migrations and in contrast to the enzymes catalyzing reversible carbon skeleton rearrangements, the dimethylbenzimidazole moiety of the cofactor is not displaced by a protein histidine upon binding to RTPR.",
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