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| | ==Crystal structure of the MutT protein in MN(II) bound holo form== | | ==Crystal structure of the MutT protein in MN(II) bound holo form== |
| - | <StructureSection load='3a6v' size='340' side='right' caption='[[3a6v]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='3a6v' size='340' side='right'caption='[[3a6v]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3a6v]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3A6V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3A6V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3a6v]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3A6V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3A6V FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3a6s|3a6s]], [[3a6t|3a6t]], [[3a6u|3a6u]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3a6s|3a6s]], [[3a6t|3a6t]], [[3a6u|3a6u]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MUTT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MUTT ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</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=3a6v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3a6v OCA], [http://pdbe.org/3a6v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3a6v RCSB], [http://www.ebi.ac.uk/pdbsum/3a6v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3a6v ProSAT]</span></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=3a6v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3a6v OCA], [https://pdbe.org/3a6v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3a6v RCSB], [https://www.ebi.ac.uk/pdbsum/3a6v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3a6v ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MUTT_ECOLI MUTT_ECOLI]] Involved in the GO system responsible for removing an oxidatively damaged form of guanine (7,8-dihydro-8-oxoguanine) from DNA and the nucleotide pool. 8-oxo-dGTP is inserted opposite dA and dC residues of template DNA with almost equal efficiency thus leading to A.T to G.C transversions. MutT specifically degrades 8-oxo-dGTP to the monophosphate.<ref>PMID:1309939</ref> <ref>PMID:15850400</ref> | + | [[https://www.uniprot.org/uniprot/MUTT_ECOLI MUTT_ECOLI]] Involved in the GO system responsible for removing an oxidatively damaged form of guanine (7,8-dihydro-8-oxoguanine) from DNA and the nucleotide pool. 8-oxo-dGTP is inserted opposite dA and dC residues of template DNA with almost equal efficiency thus leading to A.T to G.C transversions. MutT specifically degrades 8-oxo-dGTP to the monophosphate.<ref>PMID:1309939</ref> <ref>PMID:15850400</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[7%2C8-dihydro-8-oxoguanine triphosphatase|7%2C8-dihydro-8-oxoguanine triphosphatase]] | + | *[[7%2C8-dihydro-8-oxoguanine triphosphatase 3D structures|7%2C8-dihydro-8-oxoguanine triphosphatase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Ecoli]] | | [[Category: Ecoli]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Nakamura, T]] | | [[Category: Nakamura, T]] |
| | [[Category: Yamagata, Y]] | | [[Category: Yamagata, Y]] |
| Structural highlights
Function
[MUTT_ECOLI] Involved in the GO system responsible for removing an oxidatively damaged form of guanine (7,8-dihydro-8-oxoguanine) from DNA and the nucleotide pool. 8-oxo-dGTP is inserted opposite dA and dC residues of template DNA with almost equal efficiency thus leading to A.T to G.C transversions. MutT specifically degrades 8-oxo-dGTP to the monophosphate.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Escherichia coli MutT hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, an event that can prevent the misincorporation of 8-oxoguanine opposite adenine in DNA. Of the several enzymes that recognize 8-oxoguanine, MutT exhibits high substrate specificity for 8-oxoguanine nucleotides; however, the structural basis for this specificity is unknown. The crystal structures of MutT in the apo and holo forms and in the binary and ternary forms complexed with the product 8-oxo-dGMP and 8-oxo-dGMP plus Mn(2+), respectively, were determined. MutT strictly recognizes the overall conformation of 8-oxo-dGMP through a number of hydrogen bonds. This recognition mode revealed that 8-oxoguanine nucleotides are discriminated from guanine nucleotides by not only the hydrogen bond between the N7-H and Odelta (N119) atoms but also by the syn glycosidic conformation that 8-oxoguanine nucleotides prefer. Nevertheless, these discrimination factors cannot by themselves explain the roughly 34,000-fold difference between the affinity of MutT for 8-oxo-dGMP and dGMP. When the binary complex of MutT with 8-oxo-dGMP is compared with the ligand-free form, ordering and considerable movement of the flexible loops surrounding 8-oxo-dGMP in the binary complex are observed. These results indicate that MutT specifically recognizes 8-oxoguanine nucleotides by the ligand-induced conformational change.
Structural and dynamic features of the MutT protein in the recognition of nucleotides with the mutagenic 8-oxoguanine base.,Nakamura T, Meshitsuka S, Kitagawa S, Abe N, Yamada J, Ishino T, Nakano H, Tsuzuki T, Doi T, Kobayashi Y, Fujii S, Sekiguchi M, Yamagata Y J Biol Chem. 2010 Jan 1;285(1):444-52. Epub 2009 Oct 28. PMID:19864691[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Maki H, Sekiguchi M. MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis. Nature. 1992 Jan 16;355(6357):273-5. PMID:1309939 doi:http://dx.doi.org/10.1038/355273a0
- ↑ Ito R, Hayakawa H, Sekiguchi M, Ishibashi T. Multiple enzyme activities of Escherichia coli MutT protein for sanitization of DNA and RNA precursor pools. Biochemistry. 2005 May 3;44(17):6670-4. PMID:15850400 doi:http://dx.doi.org/10.1021/bi047550k
- ↑ Nakamura T, Meshitsuka S, Kitagawa S, Abe N, Yamada J, Ishino T, Nakano H, Tsuzuki T, Doi T, Kobayashi Y, Fujii S, Sekiguchi M, Yamagata Y. Structural and dynamic features of the MutT protein in the recognition of nucleotides with the mutagenic 8-oxoguanine base. J Biol Chem. 2010 Jan 1;285(1):444-52. Epub 2009 Oct 28. PMID:19864691 doi:10.1074/jbc.M109.066373
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