Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 9 July 2004:
Vol. 305. no. 5681, pp. 245 - 248
DOI: 10.1126/science.1098419
Prev | Table of Contents | Next

Reports

The Radical Site in Chlamydial Ribonucleotide Reductase Defines a New R2 Subclass

Martin Högbom,1*{dagger} Pål Stenmark,1* Nina Voevodskaya,2 Grant McClarty,3 Astrid Gräslund,2 Pär Nordlund1{ddagger}

Ribonucleotide reductase (RNR) synthesizes the deoxyribonucleotides for DNA synthesis. The R2 protein of normal class I ribonucleotide reductases contains a diiron site that produces a stable tyrosyl free radical, essential for enzymatic activity. Structural and electron paramagnetic resonance studies of R2 from Chlamydia trachomatis reveal a protein lacking a tyrosyl radical site. Instead, the protein yields an iron-coupled radical upon reconstitution. The coordinating structure of the diiron site is similar to that of diiron oxidases/monoxygenases and supports a role for this radical in the RNR mechanism. The specific ligand pattern in the C. trachomatis R2 metal site characterizes a new group of R2 proteins that so far has been found in eight organisms, three of which are human pathogens.

1 Department of Biochemistry and Biophysics, Stockholm University, Roslagstullsbacken 15, Albanova University Center, SE-10691 Stockholm, Sweden.
2 Department of Biochemistry and Biophysics, Stockholm University, Arrhenius Laboratories for Natural Sciences A3, SE-10691 Stockholm, Sweden.
3 Department of Medical Microbiology, University of Manitoba and National Microbiology Laboratory, Health Canada, Winnipeg, Manitoba R3E 0W3, Canada.



Note added in proof: Recently, genome analysis was performed of a chlamydiae-related symbiont of free-living amoebae (34). This organism is believed to share a common ancestor with pathogenic chlamydiae but contains a normal R2 protein. This is consistent with the hypothesis that the new class Ic R2 developed in response to a more elaborate immune response.

* These authors contributed equally to this work.

{dagger} Present address: Department of Cell and Molecular Biology, Uppsala University, Biomedical Center Box 596, SE-751 24, Uppsala, Sweden.

{ddagger} To whom correspondence should be addressed. E-mail: par.nordlund{at}dbb.su.se

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A Mycobacterium tuberculosis ligand-binding Mn/Fe protein reveals a new cofactor in a remodeled R2-protein scaffold.
C. S. Andersson and M. Hogbom (2009)
PNAS 106, 5633-5638
   Abstract »    Full Text »    PDF »
Redox Intermediates of the Mn-Fe Site in Subunit R2 of Chlamydia trachomatis Ribonucleotide Reductase: AN X-RAY ABSORPTION AND EPR STUDY.
N. Voevodskaya, F. Lendzian, O. Sanganas, A. Grundmeier, A. Graslund, and M. Haumann (2009)
J. Biol. Chem. 284, 4555-4566
   Abstract »    Full Text »    PDF »
Function and Regulation of Class I Ribonucleotide Reductase-Encoding Genes in Mycobacteria.
M. B. Mowa, D. F. Warner, G. Kaplan, B. D. Kana, and V. Mizrahi (2009)
J. Bacteriol. 191, 985-995
   Abstract »    Full Text »    PDF »
From the Cover: Swapping metals in Fe- and Mn-dependent dioxygenases: Evidence for oxygen activation without a change in metal redox state.
J. P. Emerson, E. G. Kovaleva, E. R. Farquhar, J. D. Lipscomb, and L. Que Jr. (2008)
PNAS 105, 7347-7352
   Abstract »    Full Text »    PDF »
A Manganese(IV)/Iron(III) Cofactor in Chlamydia trachomatis Ribonucleotide Reductase.
W. Jiang, D. Yun, L. Saleh, E. W. Barr, G. Xing, L. M. Hoffart, M.-A. Maslak, C. Krebs, and J. M. Bollinger Jr. (2007)
Science 316, 1188-1191
   Abstract »    Full Text »    PDF »
Chlamydial ribonucleotide reductase: Tyrosyl radical function in catalysis replaced by the FeIII-FeIV cluster.
N. Voevodskaya, A.-J. Narvaez, V. Domkin, E. Torrents, L. Thelander, and A. Graslund (2006)
PNAS 103, 9850-9854
   Abstract »    Full Text »    PDF »
A dityrosyl-diiron radical cofactor center is essential for human ribonucleotide reductases.
B. Zhou, J. Shao, L. Su, Y.-C. Yuan, C. Qi, J. Shih, B. Xi, B. Chu, and Y. Yen (2005)
Mol. Cancer Ther. 4, 1830-1836
   Abstract »    Full Text »    PDF »
A New Tyrosyl Radical on Phe208 as Ligand to the Diiron Center in Escherichia coli Ribonucleotide Reductase, Mutant R2-Y122H: COMBINED X-RAY DIFFRACTION AND EPR/ENDOR STUDIES.
M. Kolberg, D. T. Logan, G. Bleifuss, S. Potsch, B.-M. Sjoberg, A. Graslund, W. Lubitz, G. Lassmann, and F. Lendzian (2005)
J. Biol. Chem. 280, 11233-11246
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)