4iem | pdb_00004iem

Human apurinic/apyrimidinic endonuclease (APE1) with product DNA and Mg2+

spinqualitylabelsall models 4iem, resolution 2.39Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4iem is a 16 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG, NA NonStd Res: 3DR Related: 4iek Gene: APE, APE1, APEX, APEX1, APX, HAP1, REF1 (Homo sapiens) Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Non-coding apurinic/apyrimidinic (AP) sites in DNA form spontaneously and as DNA base excision repair intermediates are the most common toxic and mutagenic in vivo DNA lesion. For repair, AP sites must be processed by 5' AP endonucleases in initial stages of base repair. Human APE1 and bacterial Nfo represent the two conserved 5' AP endonuclease families in the biosphere; they both recognize AP sites and incise the phosphodiester backbone 5' to the lesion. Yet, they lack similar structures and metal ion requirements. Here, we determined and analyzed crystal structures of a 2.4 A resolution APE1-DNA product complex with Mg2+ and a 0.92 A Nfo with three metal ions. Structural and biochemical comparions of these two evolutionarily distinct enzymes, characterize key APE1 catalytic residues that are potentially functionally similar to Nfo active site components. as further tested and supported by computational analyses. We observe a Mg-water cluster in the APE1 active site, with only Glu96 forming the only direct protein coordination to the Mg2+. Despite differences in structure and metal requirements of APE1 and Nfo, comparison of their active site structures surprisingly reveals strong geometric conservation of the catalytic reaction, with APE1 catalytic side chains positioned analogously to Nfo metal positions, suggesting surprising functional equivalence between Nfo metal ions and APE1 residues. The finding that APE1 residues are positioned to substitute for Nfo metal ions is supported by the impact of mutations on activity. Collective results enlighten activities of residues, metal ions, and active site features for abasic site endonucleases. Conserved Structural Chemistry for Incision Activity in Structurally Non-homologous Apurinic/Apyirmidince Endonuclease APE1 and Endonuclease IV DNA repair enzymes.,Tsutakawa SE, Shin DS, Mol CD, Izumi T, Arvai AS, Mantha AK, Szczesny B, Ivanov IN, Hosfield DJ, Maiti B, Pique ME, Frankel KA, Hitomi K, Cunningham RP, Mitra S, Tainer JA J Biol Chem. 2013 Jan 25. PMID:23355472 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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