spacer CRYSTAL STRUCTURE OF ESCHERICHIA COLI ENDONUCLEASE IV IN COMPLEX WITH DAMAGED DNA
Primary citation
Title Structure of the DNA repair enzyme endonuclease IV and its DNA complex: double-nucleotide flipping at abasic sites and three-metal-ion catalysis.
Authors Hosfield, D.J.search; Guan, Y.search; Haas, B.J.search; Cunningham, R.P.search; Tainer, J.A.search
Journal CELL(CAMBRIDGE,MASS.)search vol:98, pag:397-408 (1999), Identifiers: PubMed ID (10458614)search DOI (10.1016/S0092-8674(00)81968-6)
Abstract Endonuclease IV is the archetype for a conserved apurinic/apyrimidinic (AP) endonuclease family that primes DNA repair synthesis by cleaving the DNA backbone 5' of AP sites. The crystal structures of Endonuclease IV and its AP-DNA complex at 1.02 and 1.55 A resolution reveal how an alpha8beta8 TIM barrel fold can bind dsDNA. Enzyme loops intercalate side chains at the abasic site, compress the DNA backbone, bend the DNA approximately 90 degrees, and promote double-nucleotide flipping to sequester the extrahelical AP site in an enzyme pocket that excludes undamaged nucleotides. These structures suggest three Zn2+ ions directly participate in phosphodiester bond cleavage and prompt hypotheses that double-nucleotide flipping and sharp bending by AP endonucleases provide exquisite damage specificity while aiding subsequent base excision repair pathway progression.
MeSH terms Amino Acid Sequencesearch, Animalssearch, Binding Sitessearch, Caenorhabditis eleganssearch, Carbon-Oxygen Lyasessearch, Computer Graphicssearch, Conserved Sequencesearch, Crystallographysearch, X-Raysearch, DNAsearch, DNA Damagesearch, DNA Repairsearch, DNA-(Apurinic or Apyrimidinic Site) Lyasesearch, Deoxyribonuclease IV (Phage T4-Induced)search, Escherichia colisearch, Escherichia coli Proteinssearch, Modelssearch, Molecularsearch, Molecular Sequence Datasearch, Nucleic Acid Conformationsearch, Protein Foldingsearch, Protein Structuresearch, Secondarysearch, Saccharomyces cerevisiaesearch, Sequence Alignmentsearch, Sequence Homologysearch, Amino Acidsearch, Zincsearch
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