A metal-binding site in the catalytic subunit of anaerobic ribonucleotide reductase

  1. Derek T. Logan*,,
  2. Etienne Mulliez,
  3. Karl-Magnus Larsson§,
  4. Sabrina Bodevin,
  5. Mohamed Atta,
  6. Pierre Emmanuel Garnaud,
  7. Britt-Marie Sjöberg, and
  8. Marc Fontecave,
  1. *Department of Molecular Biophysics, Lund University, Box 124, 221 00 Lund, Sweden; Laboratoire de Chimie et Biochimie des Centers Rédox Biologiques, Unité Mixte de Recherche, Centre National de la Recherche Scientifique/Commissariat à l'Energie Atomique/Université Joseph Fourier No. 5047, Département de Réponse et Dynamique Cellulaires–Laboratoire de Chimie Biologique, Commissariat à l'Energie Atomique Grenoble, 38054 Grenoble Cedex 9, France; and Departments of §Biochemistry and Biophysics and Molecular Biology and Functional Genomics, Stockholm University, S-106 91 Stockholm, Sweden
  1. Edited by Kenneth N. Raymond, University of California, Berkeley, CA, and approved February 11, 2003 (received for review October 24, 2002)

Abstract

A Zn(Cys)4 center has been found in the C-terminal region of the crystal structure of the anaerobic class III ribonucleotide reductase (RNR) from bacteriophage T4. The metal center is structurally related to the zinc ribbon motif and to rubredoxin and rubrerythrin. Mutant enzymes of the homologous RNR from Escherichia coli, in which the coordinating cysteines, conserved in almost all known class III RNR sequences, have been mutated into alanines, are shown to be inactive as the result of their inability to generate the catalytically essential glycyl radical. The possible roles of the metal center are discussed in relationship to the currently proposed reaction mechanism for generation of the glycyl radical in class III RNRs.

Footnotes

  • To whom correspondence should be addressed. E-mail: derek.logan{at}mbfys.lu.se or mfontecave{at}cea.fr.

  • This paper was submitted directly (Track II) to the PNAS office.

  • Data deposition: The further refined coordinates of the dGTP complex have been deposited in the Protein Data Bank, www.rcsb.org, with PDB ID code replacing entry .

  • Abbreviations:
    1. RNR, ribonucleotide reductase

    2. AdoMet, S-adenosylmethionine

    3. fldx, flavodoxin

    4. MBD, metal-binding domain

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