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Science 9 July 2004:
Vol. 305. no. 5681, pp. 245 - 248
DOI: 10.1126/science.1098419
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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

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