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| | ==Crystal structure of Mycobacterium smegmatis MutT1 in complex with ATP (I)== | | ==Crystal structure of Mycobacterium smegmatis MutT1 in complex with ATP (I)== |
| - | <StructureSection load='5xd3' size='340' side='right' caption='[[5xd3]], [[Resolution|resolution]] 1.78Å' scene=''> | + | <StructureSection load='5xd3' size='340' side='right'caption='[[5xd3]], [[Resolution|resolution]] 1.78Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5xd3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XD3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XD3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5xd3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XD3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XD3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.78Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5xd5|5xd5]], [[5xd4|5xd4]], [[5xd2|5xd2]], [[5xd1|5xd1]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=5xd3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xd3 OCA], [http://pdbe.org/5xd3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xd3 RCSB], [http://www.ebi.ac.uk/pdbsum/5xd3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xd3 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=5xd3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xd3 OCA], [https://pdbe.org/5xd3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xd3 RCSB], [https://www.ebi.ac.uk/pdbsum/5xd3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xd3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/MUTT1_MYCS2 MUTT1_MYCS2] Catalyzes the conversion of 8-oxo-dGTP to 8-oxo-dGDP, and 8-oxo-GTP to 8-oxo-GDP (PubMed:16585780, PubMed:28375146). At high enzyme concentrations, can also catalyze the conversion of 8-oxo-dGDP to 8-oxo-dGMP, and 8-oxo-GDP to 8-oxo-GMP (PubMed:28375146). In addition, catalyzes the hydrolysis of the diadenosine polyphosphates diadenosine hexaphosphate (Ap6A), diadenosine pentaphosphate (Ap5A) and diadenosine tetraphosphate (Ap4A) (PubMed:28705712).<ref>PMID:16585780</ref> <ref>PMID:28375146</ref> <ref>PMID:28705712</ref> |
| | <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 5xd3" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5xd3" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[7%2C8-dihydro-8-oxoguanine triphosphatase 3D structures|7%2C8-dihydro-8-oxoguanine triphosphatase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Arif, S M]] | + | [[Category: Large Structures]] |
| - | [[Category: Varshney, U]] | + | [[Category: Mycolicibacterium smegmatis MC2 155]] |
| - | [[Category: Vijayan, M]] | + | [[Category: Arif SM]] |
| - | [[Category: Diadenosine polyphosphate]] | + | [[Category: Varshney U]] |
| - | [[Category: Enzyme action]] | + | [[Category: Vijayan M]] |
| - | [[Category: Fluoride inhibition]]
| + | |
| - | [[Category: Histidine phosphatase domain]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Intermolecular interface binding]]
| + | |
| - | [[Category: Nudix enzyme]]
| + | |
| Structural highlights
Function
MUTT1_MYCS2 Catalyzes the conversion of 8-oxo-dGTP to 8-oxo-dGDP, and 8-oxo-GTP to 8-oxo-GDP (PubMed:16585780, PubMed:28375146). At high enzyme concentrations, can also catalyze the conversion of 8-oxo-dGDP to 8-oxo-dGMP, and 8-oxo-GDP to 8-oxo-GMP (PubMed:28375146). In addition, catalyzes the hydrolysis of the diadenosine polyphosphates diadenosine hexaphosphate (Ap6A), diadenosine pentaphosphate (Ap5A) and diadenosine tetraphosphate (Ap4A) (PubMed:28705712).[1] [2] [3]
Publication Abstract from PubMed
Diadenosine polyphosphates (ApnA, n=2-6), particularly Ap4A, are involved in several important physiological processes. The substantial sequence identity of the Nudix hydrolase domain (domain 1) of Mycobacterium smegmatis MutT1 (MsMutT1) with a known Ap4A hydrolase suggested that MsMutT1 could also hydrolyse diadenosine polyphosphates. Biochemical experiments yielded results in conformity with this suggestion, with Ap4A as the best among the substrates. ATP is a product in all experiments; small amounts of ADP were also observed in the experiments involving Ap4A and Ap6A. Hydrolysis was inhibited by fluoride ions in all cases. The mechanism of action and its inhibition in relation to ApnA were explored through the X-ray analysis of the crystals of the MsMutT1 complexes with Ap5A; Ap5A and MnCl2; Ap4A; ATP; and ATP.NaF.MgCl2. The aggregation pattern of molecules in the first four crystals is similar to that found in a majority of MsMutT1-NTP crystals. Substrate molecules occupy the primary binding site and ATP occupies a site at an intermolecular interface, in the first two. ATP occupies both the sites in the third and fourth crystal. The protein-ligand interactions observed in these crystal structures lead to an explanation of the molecular mechanism of hydrolysis of ApnA by MsMutT1. The fifth crystal exhibits a new packing arrangement. The structure of the complex provides an explanation for the fluoride inhibition of the activity of the enzyme. It would thus appear that MutT1 has a major role involving the hydrolysis of diadenosine polyphosphates, which could be elucidated at the molecular level.
Hydrolysis of diadenosine polyphosphates. Exploration of an additional role of Mycobacterium smegmatis MutT1.,Arif SM, Varshney U, Vijayan M J Struct Biol. 2017 Jul 10. pii: S1047-8477(17)30122-3. doi:, 10.1016/j.jsb.2017.07.002. PMID:28705712[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dos Vultos T, Blázquez J, Rauzier J, Matic I, Gicquel B. Identification of Nudix hydrolase family members with an antimutator role in Mycobacterium tuberculosis and Mycobacterium smegmatis. J Bacteriol. 2006 Apr;188(8):3159-61. PMID:16585780 doi:10.1128/JB.188.8.3159-3161.2006
- ↑ Arif SM, Patil AG, Varshney U, Vijayan M. Biochemical and structural studies of Mycobacterium smegmatis MutT1, a sanitization enzyme with unusual modes of association. Acta Crystallogr D Struct Biol. 2017 Apr 1;73(Pt 4):349-364. doi:, 10.1107/S2059798317002534. Epub 2017 Mar 31. PMID:28375146 doi:http://dx.doi.org/10.1107/S2059798317002534
- ↑ Arif SM, Varshney U, Vijayan M. Hydrolysis of diadenosine polyphosphates. Exploration of an additional role of Mycobacterium smegmatis MutT1. J Struct Biol. 2017 Jul 10. pii: S1047-8477(17)30122-3. doi:, 10.1016/j.jsb.2017.07.002. PMID:28705712 doi:http://dx.doi.org/10.1016/j.jsb.2017.07.002
- ↑ Arif SM, Varshney U, Vijayan M. Hydrolysis of diadenosine polyphosphates. Exploration of an additional role of Mycobacterium smegmatis MutT1. J Struct Biol. 2017 Jul 10. pii: S1047-8477(17)30122-3. doi:, 10.1016/j.jsb.2017.07.002. PMID:28705712 doi:http://dx.doi.org/10.1016/j.jsb.2017.07.002
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