3gx4

Crystal Structure Analysis of S. Pombe ATL in complex with DNA

spinqualitylabelsall models 3gx4, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3gx4 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. Method: X-ray diffraction, Resolution 2.7Å Ligands: 6OG, NCO 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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Alkyltransferase-like proteins (ATLs) share functional motifs with the cancer chemotherapy target O(6)-alkylguanine-DNA alkyltransferase (AGT) and paradoxically protect cells from the biological effects of DNA alkylation damage, despite lacking the reactive cysteine and alkyltransferase activity of AGT. Here we determine Schizosaccharomyces pombe ATL structures without and with damaged DNA containing the endogenous lesion O(6)-methylguanine or cigarette-smoke-derived O(6)-4-(3-pyridyl)-4-oxobutylguanine. These results reveal non-enzymatic DNA nucleotide flipping plus increased DNA distortion and binding pocket size compared to AGT. Our analysis of lesion-binding site conservation identifies new ATLs in sea anemone and ancestral archaea, indicating that ATL interactions are ancestral to present-day repair pathways in all domains of life. Genetic connections to mammalian XPG (also known as ERCC5) and ERCC1 in S. pombe homologues Rad13 and Swi10 and biochemical interactions with Escherichia coli UvrA and UvrC combined with structural results reveal that ATLs sculpt alkylated DNA to create a genetic and structural intersection of base damage processing with nucleotide excision repair. Flipping of alkylated DNA damage bridges base and nucleotide excision repair.,Tubbs JL, Latypov V, Kanugula S, Butt A, Melikishvili M, Kraehenbuehl R, Fleck O, Marriott A, Watson AJ, Verbeek B, McGown G, Thorncroft M, Santibanez-Koref MF, Millington C, Arvai AS, Kroeger MD, Peterson LA, Williams DM, Fried MG, Margison GP, Pegg AE, Tainer JA Nature. 2009 Jun 11;459(7248):808-13. PMID:19516334 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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