Document Detail


Products of the inactivation of ribonucleoside diphosphate reductase from Escherichia coli with 2'-azido-2'-deoxyuridine 5'-diphosphate.
MedLine Citation:
PMID:  3307907     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ribonucleoside diphosphate reductase (RDPR) from Escherichia coli was completely inactivated by 1 equiv of the mechanism-based inhibitor 2'-azido-2'-deoxyuridine 5'-diphosphate (N3UDP). Incubation of RDPR with [3'-3H]N3UDP resulted in 0.2 mol of 3H released to solvent per mole of enzyme inactivated, indicating that cleavage of the 3' carbon-hydrogen bond occurred in the reaction. Incubation of RDPR with [beta-32P]N3UDP resulted in stoichiometric production of inorganic pyrophosphate. One equivalent of uracil was eliminated from N3UDP, but no azide release was detected. Analysis of the reaction of RDPR with [15N3]N3UDP by mass spectrometry revealed that the azide moiety was converted to 0.9 mol of nitrogen gas per mole of enzyme inactivated. The tyrosyl radical of the B2 subunit was destroyed during the inactivation by N3UDP as reported previously [Sjöberg, B.-M., Gräslund, A., & Eckstein, F. (1983) J. Biol. Chem. 258, 8060-8067], while the specific activity of the B1 subunit was reduced by half. Incubation of [5'-3H]N3UDP with RDPR resulted in stoichiometric covalent radiolabeling of the enzyme. Separation of the enzyme's subunits by chromatofocusing revealed that the modification was specific for the B1 subunit.
Authors:
S P Salowe; M A Ator; J Stubbe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemistry     Volume:  26     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  1987 Jun 
Date Detail:
Created Date:  1987-11-16     Completed Date:  1987-11-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3408-16     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, College of Agriculture and Life Sciences, University of Wisconsin-Madison 53706.
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MeSH Terms
Descriptor/Qualifier:
Affinity Labels / pharmacology*
Azides / pharmacology*
Deoxyuracil Nucleotides / pharmacology*
Escherichia coli / enzymology*
Hydroxyurea / pharmacology
Kinetics
Protein Binding
Ribonucleoside Diphosphate Reductase / antagonists & inhibitors*
Ribonucleotide Reductases / antagonists & inhibitors*
Tritium
Grant Support
ID/Acronym/Agency:
AM 01222/AM/NIADDK NIH HHS; GM 29595/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Affinity Labels; 0/Azides; 0/Deoxyuracil Nucleotides; 10028-17-8/Tritium; 127-07-1/Hydroxyurea; 36792-49-1/2'-azido-2'-deoxyuridine 5'-diphosphate; EC 1.17.4.-/Ribonucleotide Reductases; EC 1.17.4.1/Ribonucleoside Diphosphate Reductase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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