View source for 4wxd


==Crystal structure of Mycobacterium tuberculosis OGT-R37K==
<StructureSection load='4wxd' size='340' side='right'caption='[[4wxd]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4wxd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WXD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WXD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4wxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wxd OCA], [https://pdbe.org/4wxd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wxd RCSB], [https://www.ebi.ac.uk/pdbsum/4wxd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wxd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/OGT_MYCTU 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).
<div style="background-color:#fffaf0;">
== 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<ref>PMID:26512127</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4wxd" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Garavaglia S]]
[[Category: Miggiano R]]
[[Category: Rizzi M]]
[[Category: Rossi F]]