5gg8: Difference between revisions
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The | ==Crystal structure of Mycobacterium smegmatis MutT1 in complex with 8-oxo-dGTP, 8-oxo-dGMP and pyrophosphate (II)== | ||
<StructureSection load='5gg8' size='340' side='right'caption='[[5gg8]], [[Resolution|resolution]] 1.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5gg8]] 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=5GG8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GG8 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]] 1.85Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8DG:8-OXO-2-DEOXYGUANOSINE-5-TRIPHOSPHATE'>8DG</scene>, <scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</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=5gg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gg8 OCA], [https://pdbe.org/5gg8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gg8 RCSB], [https://www.ebi.ac.uk/pdbsum/5gg8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gg8 ProSAT]</span></td></tr> | |||
</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;"> | |||
== Publication Abstract from PubMed == | |||
Mycobacterium smegmatis MutT1, which is made up of a Nudix domain (domain 1) and a histidine phosphatase domain (domain 2), efficiently hydrolyses 8-oxo-GTP and 8-oxo-dGTP to the corresponding nucleoside diphosphates and phosphate in the presence of magnesium ions. Domain 1 alone hydrolyses nucleoside triphosphates less efficiently. Under high concentrations and over long periods, the full-length enzyme as well as domain 1 catalyses the hydrolysis of the nucleoside triphosphates to the respective nucleoside monophosphates and pyrophosphate. The role of domain 2 appears to be limited to speeding up the reaction. Crystal structures of the apoenzyme and those of ligand-bound enzyme prepared in the presence of 8-oxo-GTP or 8-oxo-dGTP and different concentrations of magnesium were determined. In all of the structures except one, the molecules arrange themselves in a head-to-tail fashion in which domain 1 is brought into contact with domain 2 (trans domain 2) of a neighbouring molecule. The binding site for NTP (site A) is almost exclusively made up of residues from domain 1, while those for NDP (site B) and NMP (site C) are at the interface between domain 1 and trans domain 2 in an unusual instance of intermolecular interactions leading to binding sites. Protein-ligand interactions at site A lead to a proposal for the mechanism of hydrolysis of NTP to NDP and phosphate. A small modification in site A in the crystal which does not exhibit the head-to-tail arrangement appears to facilitate the production of NMP and pyrophosphate from NTP. The two arrangements could be in dynamic equilibrium in the cellular milieu. | |||
Biochemical and structural studies of Mycobacterium smegmatis MutT1, a sanitization enzyme with unusual modes of association.,Arif SM, Patil AG, Varshney U, Vijayan M Acta Crystallogr D Struct Biol. 2017 Apr 1;73(Pt 4):349-364. doi:, 10.1107/S2059798317002534. Epub 2017 Mar 31. PMID:28375146<ref>PMID:28375146</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5gg8" style="background-color:#fffaf0;"></div> | ||
[[Category: Arif | |||
[[Category: Patil | ==See Also== | ||
[[Category: Varshney | *[[7%2C8-dihydro-8-oxoguanine triphosphatase 3D structures|7%2C8-dihydro-8-oxoguanine triphosphatase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycolicibacterium smegmatis MC2 155]] | |||
[[Category: Arif SM]] | |||
[[Category: Patil AG]] | |||
[[Category: Varshney U]] | |||
[[Category: Vijayan M]] | |||
Latest revision as of 14:30, 2 August 2023
Crystal structure of Mycobacterium smegmatis MutT1 in complex with 8-oxo-dGTP, 8-oxo-dGMP and pyrophosphate (II)Crystal structure of Mycobacterium smegmatis MutT1 in complex with 8-oxo-dGTP, 8-oxo-dGMP and pyrophosphate (II)
Structural highlights
FunctionMUTT1_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 PubMedMycobacterium smegmatis MutT1, which is made up of a Nudix domain (domain 1) and a histidine phosphatase domain (domain 2), efficiently hydrolyses 8-oxo-GTP and 8-oxo-dGTP to the corresponding nucleoside diphosphates and phosphate in the presence of magnesium ions. Domain 1 alone hydrolyses nucleoside triphosphates less efficiently. Under high concentrations and over long periods, the full-length enzyme as well as domain 1 catalyses the hydrolysis of the nucleoside triphosphates to the respective nucleoside monophosphates and pyrophosphate. The role of domain 2 appears to be limited to speeding up the reaction. Crystal structures of the apoenzyme and those of ligand-bound enzyme prepared in the presence of 8-oxo-GTP or 8-oxo-dGTP and different concentrations of magnesium were determined. In all of the structures except one, the molecules arrange themselves in a head-to-tail fashion in which domain 1 is brought into contact with domain 2 (trans domain 2) of a neighbouring molecule. The binding site for NTP (site A) is almost exclusively made up of residues from domain 1, while those for NDP (site B) and NMP (site C) are at the interface between domain 1 and trans domain 2 in an unusual instance of intermolecular interactions leading to binding sites. Protein-ligand interactions at site A lead to a proposal for the mechanism of hydrolysis of NTP to NDP and phosphate. A small modification in site A in the crystal which does not exhibit the head-to-tail arrangement appears to facilitate the production of NMP and pyrophosphate from NTP. The two arrangements could be in dynamic equilibrium in the cellular milieu. Biochemical and structural studies of Mycobacterium smegmatis MutT1, a sanitization enzyme with unusual modes of association.,Arif SM, Patil AG, Varshney U, Vijayan M Acta Crystallogr D Struct Biol. 2017 Apr 1;73(Pt 4):349-364. doi:, 10.1107/S2059798317002534. Epub 2017 Mar 31. PMID:28375146[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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