Atomic structure of the DNA repair [4Fe-4S] enzyme endonuclease III.

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