Structure of the high-valent FeIIIFeIV state in ribonucleotide reductase (RNR) of Chlamydia trachomatis--combined EPR, 57Fe-, 1H-ENDOR and X-ray studies

Biochim Biophys Acta. 2007 Oct;1774(10):1254-63. doi: 10.1016/j.bbapap.2007.07.001. Epub 2007 Jul 17.

Abstract

A recently discovered subgroup of class I ribonucleotide reductase (RNR) found in the infectious bacterium Chlamydia trachomatis (C. trachomatis) was shown to exhibit a high-valent Fe(III)Fe(IV) center instead of the tyrosyl radical observed normally in all class I RNRs. The X-ray structure showed that C. trachomatis WT RNR has a phenylalanine at the position of the active tyrosine in Escherichia coli RNR. In this paper the X-ray structure of variant F127Y is presented, where the tyrosine is restored. Using (1)H- and (57)Fe-ENDOR spectroscopy it is shown, that in WT and variants F127Y and Y129F of C. trachomatis RNR, the Fe(III)Fe(IV) center is virtually identical with the short-lived intermediate X observed during the iron oxygen reconstitution reaction in class I RNR from E. coli. The experimental data are consistent with a recent theoretical model for X, proposing two bridging oxo ligands and one terminal water ligand. A surprising extension of the lifetime of the Fe(III)Fe(IV) state in C. trachomatis from a few seconds to several hours at room temperature was observed under catalytic conditions in the presence of substrate. These findings suggest a possible new role for the Fe(III)Fe(IV) state also in other class I RNR, during the catalytic radical transfer reaction, by which the substrate turnover is started.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution / genetics
  • Chlamydia trachomatis / enzymology*
  • Chlamydia trachomatis / genetics
  • Crystallography, X-Ray
  • Electron Spin Resonance Spectroscopy
  • Ferric Compounds / chemistry*
  • Ferrous Compounds / chemistry*
  • Point Mutation
  • Ribonucleotide Reductases / chemistry*
  • Ribonucleotide Reductases / genetics
  • Substrate Specificity / genetics

Substances

  • Ferric Compounds
  • Ferrous Compounds
  • Ribonucleotide Reductases
  • ribonucleotide reductase R2 subunit