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Science 25 May 2007:
Vol. 316. no. 5828, pp. 1188 - 1191
DOI: 10.1126/science.1141179
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Reports

A Manganese(IV)/Iron(III) Cofactor in Chlamydia trachomatis Ribonucleotide Reductase

Wei Jiang,1 Danny Yun,1* Lana Saleh,1{dagger} Eric W. Barr,1 Gang Xing,1 Lee M. Hoffart,1 Monique-Anne Maslak,1 Carsten Krebs,1,2{ddagger} J. Martin Bollinger, Jr.1,2{ddagger}

In a conventional class I ribonucleotide reductase (RNR), a diiron(II/II) cofactor in the R2 subunit reacts with oxygen to produce a diiron(III/IV) intermediate, which generates a stable tyrosyl radical (Ybullet). The Ybullet reversibly oxidizes a cysteine residue in the R1 subunit to a cysteinyl radical (Cbullet), which abstracts the 3'-hydrogen of the substrate to initiate its reduction. The RNR from Chlamydia trachomatis lacks the Ybullet, and it had been proposed that the diiron(III/IV) complex in R2 directly generates the Cbullet in R1. By enzyme activity measurements and spectroscopic methods, we show that this RNR actually uses a previously unknown stable manganese(IV)/iron(III) cofactor for radical initiation.

1 Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA.
2 Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA.

* Present address: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

{dagger} Present address: New England Biolabs, 240 County Road, Ipswich, MA 01938, USA.

{ddagger} To whom correspondence should be addressed. E-mail: ckrebs{at}psu.edu (C.K.), jmb21{at}psu.edu (J.M.B.)

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