3d4v | pdb_00003d4v

Crystal Structure of an AlkA Host/Guest Complex N7MethylGuanine:Cytosine Base Pair

spinqualitylabelsall models 3d4v, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3d4v is a 8 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: FMG Gene: alkA, aidA, b2068, JW2053 ("Bacillus coli" Migula 1895) Activity: DNA-3-methyladenine glycosylase II, with EC number 3.2.2.21 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [3MG2_ECOLI] Hydrolysis of the deoxyribose N-glycosidic bond to excise 3-methyladenine, 3-methylguanine, 7-methylguanine, O2-methylthymine, and O2-methylcytosine from the damaged DNA polymer formed by alkylation lesions. 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 The predominant product of aberrant DNA methylation is the genotoxic lesion N7-methyl-2'-deoxyguanosine (m7dG). M7dG is recognized and excised by lesion-specific DNA glycosylases, namely AlkA in E. coli and Aag in humans. Structural studies of m7dG recognition and catalysis by these enzymes have been hampered due to a lack of efficient means by which to incorporate the chemically labile m7dG moiety site-specifically into DNA on a preparative scale. Here we report a solution to this problem. We stabilized the lesion toward acid-catalyzed and glycosylase-catalyzed depurination by 2'-fluorination and toward base-catalyzed degradation using mild, nonaqueous conditions in the DNA deprotection reaction. Duplex DNA containing 2'-fluoro-m7dG (Fm7dG) cocrystallized with AlkA as a host-guest complex in which the lesion-containing segment of DNA was nearly devoid of protein contacts, thus enabling the first direct visualization of the N7-methylguanine lesion nucleobase in DNA. The structure reveals that the base-pairing mode of Fm7dG:C is nearly identical to that of G:C, and Fm7dG does not induce any apparent structural disturbance of the duplex structure. These observations suggest that AlkA and Aag must perform a structurally invasive interrogation of DNA in order to detect the presence of intrahelical m7dG lesions. Synthesis and structure of duplex DNA containing the genotoxic nucleobase lesion N7-methylguanine.,Lee S, Bowman BR, Ueno Y, Wang S, Verdine GL J Am Chem Soc. 2008 Sep 3;130(35):11570-1. Epub 2008 Aug 8. PMID:18686953 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA glycosylase

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