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| | ==Crystal structure of Mycobacterium tuberculosis OGT in complex with DNA== | | ==Crystal structure of Mycobacterium tuberculosis OGT in complex with DNA== |
| - | <StructureSection load='4wx9' size='340' side='right' caption='[[4wx9]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='4wx9' size='340' side='right'caption='[[4wx9]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4wx9]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WX9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WX9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4wx9]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WX9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=E1X:PHOSPHORIC+ACID+MONO-[5-(1-ETHYL-2,6-DIOXO-1,2,3,6-TETRAHYDRO-PURIN-9-YL)-3-HYDROXY-TETRAHYDRO-FURAN-2-YLMETHYL]ESTER'>E1X</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=E1X:PHOSPHORIC+ACID+MONO-[5-(1-ETHYL-2,6-DIOXO-1,2,3,6-TETRAHYDRO-PURIN-9-YL)-3-HYDROXY-TETRAHYDRO-FURAN-2-YLMETHYL]ESTER'>E1X</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=4wx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wx9 OCA], [https://pdbe.org/4wx9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wx9 RCSB], [https://www.ebi.ac.uk/pdbsum/4wx9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wx9 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ogt, Rv1316c, MTCY130.01c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methylated-DNA--[protein]-cysteine_S-methyltransferase Methylated-DNA--[protein]-cysteine S-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.63 2.1.1.63] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4wx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wx9 OCA], [http://pdbe.org/4wx9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wx9 RCSB], [http://www.ebi.ac.uk/pdbsum/4wx9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wx9 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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). | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4wx9" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4wx9" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Myctu]] | + | [[Category: Large Structures]] |
| - | [[Category: Garavaglia, S]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Miggiano, R]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Rizzi, M]] | + | [[Category: Garavaglia S]] |
| - | [[Category: Rossi, F]] | + | [[Category: Miggiano R]] |
| - | [[Category: Alkylated dna-protein alkyltransferase]] | + | [[Category: Rizzi M]] |
| - | [[Category: Direct dna damage reversal]] | + | [[Category: Rossi F]] |
| - | [[Category: Protein-dna complex]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
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.
See Also
References
- ↑ 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
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