4hdu

Crystal structure of S. pombe ATL1 in complex with damaged DNA containing 2-aminopurine

spinqualitylabelsall models 4hdu, resolution 2.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hdu is a 3 chain structure with sequence from Schizosaccharomyces pombe. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 2PR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ATL1_SCHPO Acts as a DNA damage recognition factor. Required for DNA repair from mutagenic O(6)-alkylguanine adducts. Binds O(6)-alkylguanine lesions providing a signal for other DNA repair pathways. Publication Abstract from PubMed Alkyltransferase-like (ATL) proteins in Schizosaccharomyces pombe (Atl1) and Thermus thermophilus (TTHA1564) protect against the adverse effects of DNA alkylation damage by flagging O(6)-alkylguanine lesions for nucleotide excision repair (NER). We show that both ATL proteins bind with high affinity to oligodeoxyribonucleotides containing O(6)-alkylguanines differing in size, polarity, and charge of the alkyl group. However, Atl1 shows a greater ability than TTHA1564 to distinguish between O(6)-alkylguanine and guanine and in an unprecedented mechanism uses Arg69 to probe the electrostatic potential surface of O(6)-alkylguanine, as determined using molecular mechanics calculations. An unexpected consequence of this feature is the recognition of 2,6-diaminopurine and 2-aminopurine, as confirmed in crystal structures of respective Atl1-DNA complexes. O(6)-Alkylguanine and guanine discrimination is diminished for Atl1 R69A and R69F mutants, and S. pombe R69A and R69F mutants are more sensitive toward alkylating agent toxicity, revealing the key role of Arg69 in identifying O(6)-alkylguanines critical for NER recognition. Alkyltransferase-like protein (Atl1) distinguishes alkylated guanines for DNA repair using cation-pi interactions.,Wilkinson OJ, Latypov V, Tubbs JL, Millington CL, Morita R, Blackburn H, Marriott A, McGown G, Thorncroft M, Watson AJ, Connolly BA, Grasby JA, Masui R, Hunter CA, Tainer JA, Margison GP, Williams DM Proc Natl Acad Sci U S A. 2012 Nov 13;109(46):18755-60. doi:, 10.1073/pnas.1209451109. Epub 2012 Oct 29. PMID:23112169 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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