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Atomic-structure of the DNA-repair 4fe-4s enzyme endonuclease-iii

Academic Article
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Overview

authors

  • Kuo, C. F.
  • McRee, Duncan
  • Fisher, C. L.
  • Ohandley, S. F.
  • Cunningham, R. P.
  • Tainer, John

publication date

  • October 1992

journal

  • Science  Journal

abstract

  • The crystal structure of the DNA repair enzyme endonuclease III, which recognizes and cleaves DNA at damaged bases, has been solved to 2.0 angstrom resolution with an R factor of 0.185. This iron-sulfur [4Fe-4S] enzyme is elongated and bilobal with a deep cleft separating two similarly sized domains: a novel, sequence-continuous, six-helix domain (residues 22 to 132) and a Greek-key, four-helix domain formed by the amino-terminal and three carboxyl-terminal helices (residues 1 to 21 and 133 to 211) together with the [4Fe-4S] cluster. The cluster is bound entirely within the carboxyl-terminal loop with a ligation pattern (Cys-X6-Cys-X2-Cys-X5-Cys) distinct from all other known [4Fe-4S] proteins. Sequence conservation and the positive electrostatic potential of conserved regions identify a surface suitable for binding duplex B-DNA across the long axis of the enzyme, matching a 46 angstrom length of protected DNA. The primary role of the [4Fe-4S] cluster appears to involve positioning conserved basic residues for interaction with the DNA phosphate backbone. The crystallographically identified inhibitor binding region, which recognizes the damaged base thymine glycol, is a seven-residue beta-hairpin (residues 113 to 119). Location and side chain orientation at the base of the inhibitor binding site implicate Glu112 in the N-glycosylase mechanism and Lys120 in the beta-elimination mechanism. Overall, the structure reveals an unusual fold and a new biological function for [4Fe-4S] clusters and provides a structural basis for studying recognition of damaged DNA and the N-glycosylase and apurinic/apyrimidinic-lyase mechanisms.

subject areas

  • Bacterial Proteins
  • Base Sequence
  • Crystallography
  • Cysteine
  • DNA Repair
  • DNA-Binding Proteins
  • Deoxyribonuclease (Pyrimidine Dimer)
  • Endodeoxyribonucleases
  • Iron-Sulfur Proteins
  • Models, Molecular
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • X-Ray Diffraction
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Identity

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.1411536

PubMed ID

  • 1411536
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Additional Document Info

start page

  • 434

end page

  • 440

volume

  • 258

issue

  • 5081

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