4g4n

MutM containing M77A mutation bound to undamaged DNA

spinqualitylabelsall models 4g4n, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4g4n is a 3 chain structure with sequence from Atcc 12980. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ZN NonStd Res: TX2 Related: 4g4o, 4g4q, 4g4r Gene: mutM (ATCC 12980) Activity: DNA-formamidopyrimidine glycosylase, with EC number 3.2.2.23 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [P84131_GEOSE] Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG). Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates (By similarity).[HAMAP-Rule:MF_00103][SAAS:SAAS020629_004_120556] Publication Abstract from PubMed MutM is a bacterial DNA glycosylase that serves as the first line of defense against the highly mutagenic 8-oxoguanine (oxoG) lesion, catalyzing glycosidic bond cleavage of oxoG to initiate base excision DNA repair. Previous work has shown that MutM actively interrogates DNA for the presence of an intrahelical oxoG lesion. This interrogation process involves significant buckling and bending of the DNA to promote extrusion of oxoG from the duplex. Structural snapshots have revealed several different highly conserved residues that are prominently inserted into the duplex in the vicinity of the target oxoG before and after base extrusion has occurred. However, the roles of these helix-invading residues during the lesion recognition and base extrusion process remain unclear. In this study we set out to probe the function of residues Phe114 and Met77 in oxoG recognition and repair. Here we report a detailed biochemical and structural characterization of MutM variants containing either a F114A or M77A mutation, both of which showed significant decreases in the efficiency of oxoG repair. These data reveal that Met77 plays an important role in stabilizing the lesion-extruded conformation of the DNA. Phe114, on the other hand, appears to destabilize the intrahelical state of the oxoG lesion, primarily by buckling the target base-pair. We report the observation of a completely unexpected interaction state, in which the target base-pair is ruptured but remains fully intrahelical; this structure vividly illustrates the disruptive influence of MutM on the target base-pair. Structural and biochemical analysis of DNA helix-invasion by the bacterial 8-oxoguanine DNA glycosylase MutM.,Sung RJ, Zhang M, Qi Y, Verdine GL J Biol Chem. 2013 Feb 12. PMID:23404556 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA glycosylase

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