4wx9 | pdb_00004wx9

Crystal structure of Mycobacterium tuberculosis OGT in complex with DNA

spinqualitylabelsall models 4wx9, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4wx9 is a 5 chain structure with sequence from Mycobacterium tuberculosis H37Rv and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3Å Ligands: E1X, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function OGT_MYCTU Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) in DNA. Repairs alkylated guanine in DNA by stoichiometrically transferring the alkyl group at the O-6 position to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated (By similarity). Publication Abstract from PubMed Mycobacterium tuberculosis O 6-methylguanine-DNA methyltransferase ( Mt OGT) contributes to protect the bacterial GC-rich genome from the pro-mutagenic potential of O 6-methylated guanine in DNA. Several worldwide spread M. tuberculosis strains encode a point-mutated OGT ( Mt OGT-R37L) variant, which displays an arginine-to-leucine substitution at position 37 of the poorly functionally characterized N-terminal domain of the protein. Although the impact of this mutation on the Mt OGT activity has not yet been proven in vivo , we previously demonstrated that a recombinant Mt OGT-R37L variant performs a sub-optimal alkylated-DNA repair in vitro , suggesting a direct role for the Arg37-bearing region in catalysis. The herein reported crystal structure of Mt OGT in complex with modified DNA reveals details of the protein/protein and protein/DNA interactions occurring during alkylated-DNA binding, and the protein capability to host also unmodified bases inside the active site, in a fully extra-helical conformation. Our data provide the first experimental picture at the atomic level of a possible mode of assembling of three adjacent Mt OGT monomers on the same mono-alkylated double-stranded DNA molecule, and disclose the conformational flexibility of discrete regions of Mt OGT, including the Arg37-bearing random coil. This peculiar structural plasticity of Mt OGT could be instrumental to proper protein clustering at damaged DNA sites, as well as to protein-DNA complexes disassembling upon repair. Crystal structure of Mycobacterium tuberculosis O6-methylguanine-DNA methyltransferase protein clusters assembled onto damaged DNA.,Miggiano R, Perugino G, Ciaramella M, Serpe M, Rejman D, Pav O, Pohl R, Garavaglia S, Lahiri S, Rizzi M, Rossi F Biochem J. 2015 Oct 28. pii: BJ20150833. PMID:26512127 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA methyltransferase 3D structures

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