Summary information and primary citation

PDB-id
4wx9; DSSR-derived features in text and JSON formats
Class
transferase
Method
X-ray (3.0 Å)
Summary
Crystal structure of mycobacterium tuberculosis ogt in complex with DNA
Reference
Miggiano R, Perugino G, Ciaramella M, Serpe M, Rejman D, Pav O, Pohl R, Garavaglia S, Lahiri S, Rizzi M, Rossi F (2016): "Crystal structure of Mycobacterium tuberculosis O6-methylguanine-DNA methyltransferase protein clusters assembled on to damaged DNA." Biochem.J., 473, 123-133. doi: 10.1042/BJ20150833.
Abstract
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.

Cartoon-block schematics in six views (download the tarball)

PyMOL session file Download PDB file View in 3Dmol.js