4wxd

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Crystal structure of Mycobacterium tuberculosis OGT-R37K

Structural highlights

4wxd is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Ligands: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[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. Miggiano R, Perugino G, Ciaramella M, Serpe M, Rejman D, Pav O, Pohl R, Garavaglia S, Lahiri S, Rizzi M, Rossi F. Crystal structure of Mycobacterium tuberculosis O6-methylguanine-DNA methyltransferase protein clusters assembled onto damaged DNA. Biochem J. 2015 Oct 28. pii: BJ20150833. PMID:26512127 doi:http://dx.doi.org/10.1042/BJ20150833

Contents


PDB ID 4wxd

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