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

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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.

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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