HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Eliasson, R. Articles by Reichard, P. Search for Related Content PubMed PubMed Citation Articles by Eliasson, R. Articles by Reichard, P. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 269, Issue 42, 26116-26120, 10, 1994

Interactions of 2'-modified azido- and haloanalogs of deoxycytidine 5'- triphosphate with the anaerobic ribonucleotide reductase of Escherichia coli

R Eliasson, E Pontis, F Eckstein and P Reichard
Department of Biochemistry 1, MBB, Medical Nobel Institute, Karolinska Institutet, Stockholm, Sweden.

The anaerobic Escherichia coli ribonucleotide reductase (class III reductase) responsible for the synthesis of the deoxyribonucleotides required for anaerobic DNA replication contains an oxygen-sensitive glycyl radical (Gly-681) suggesting involvement of radical chemistry in catalysis. The amino acid sequence of this enzyme completely differs from that of earlier described aerobic class I (prototype, aerobic E. coli) and class II (prototype, Lactobacillus leichmanii) reductases that use radical chemistry but employ other means for radical generation. Here, we study the interaction between the anaerobic E. coli reductase with the 5'-triphosphates of 2'-chloro-2'-deoxycytidine, 2'-fluoro-2'-deoxycytidine, and 2'-azido-2'-deoxycytidine (N3CTP), which are mechanism-based inhibitors of class I and II reductases and, on interaction with these enzymes, decompose to base, inorganic di(tri)phosphate and 2'-methylene-3(2H)-furanone. Also, with the anaerobic E. coli reductase, the 2'-substituted nucleotides act as mechanism-based inhibitors and decompose. N3CTP scavenges the glycyl radical of the enzyme similar to the interaction of N3CDP with the tyrosyl radical of class I enzymes. However, we found no evidence for a new transient radical species as is the case with class I enzymes. Our results suggest that the chemistry at the nucleotide level for the reduction of ribose by class III enzymes is similar to the chemistry employed by class I and II enzymes.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				W. Jiang, D. Yun, L. Saleh, E. W. Barr, G. Xing, L. M. Hoffart, M.-A. Maslak, C. Krebs, and J. M. Bollinger Jr. A Manganese(IV)/Iron(III) Cofactor in Chlamydia trachomatis Ribonucleotide Reductase Science, May 25, 2007; 316(5828): 1188 - 1191. [Abstract] [Full Text] [PDF]

				S. Ollagnier, E. Mulliez, P. P. Schmidt, R. Eliasson, J. Gaillard, C. Deronzier, T. Bergman, A. Graslund, P. Reichard, and M. Fontecave Activation of the Anaerobic Ribonucleotide Reductase from Escherichia coli. THE ESSENTIAL ROLE OF THE IRON-SULFUR CENTER FOR S-ADENOSYLMETHIONINE REDUCTION J. Biol. Chem., September 26, 1997; 272(39): 24216 - 24223. [Abstract] [Full Text] [PDF]

				P. Young, J. Andersson, M. Sahlin, and B.-M. Sjoberg Bacteriophage T4 Anaerobic Ribonucleotide Reductase Contains a Stable Glycyl Radical at Position 580 J. Biol. Chem., August 23, 1996; 271(34): 20770 - 20775. [Abstract] [Full Text] [PDF]

				J. Andersson, M. Westman, M. Sahlin, and B.-M. Sjoberg Cysteines Involved in Radical Generation and Catalysis of Class III Anaerobic Ribonucleotide Reductase. A PROTEIN ENGINEERING STUDY OF BACTERIOPHAGE T4 NrdD J. Biol. Chem., June 23, 2000; 275(26): 19449 - 19455. [Abstract] [Full Text] [PDF]

				J. Andersson, S. Bodevin, M. Westman, M. Sahlin, and B.-M. Sjoberg Two Active Site Asparagines Are Essential for the Reaction Mechanism of the Class III Anaerobic Ribonucleotide Reductase from Bacteriophage T4 J. Biol. Chem., October 26, 2001; 276(44): 40457 - 40463. [Abstract] [Full Text] [PDF]