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| | ==Structural characterisation of mutant Asp39Ala of thioesterase (NmACH) from Neisseria meningitidis== | | ==Structural characterisation of mutant Asp39Ala of thioesterase (NmACH) from Neisseria meningitidis== |
| - | <StructureSection load='5t02' size='340' side='right' caption='[[5t02]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='5t02' size='340' side='right'caption='[[5t02]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5t02]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/"diplokokkus_intracellularis_meningitidis"_(sic)_weichselbaum_1887 "diplokokkus intracellularis meningitidis" (sic) weichselbaum 1887]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T02 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T02 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5t02]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_meningitidis Neisseria meningitidis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T02 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5T02 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</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]] 2.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5szu|5szu]], [[5szv|5szv]], [[5szy|5szy]], [[5szz|5szz]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ERS514298_01532, ERS514410_00397, ERS514534_01643, ERS514708_01580, ERS514851_00814 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=487 "Diplokokkus intracellularis meningitidis" (sic) Weichselbaum 1887])</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=5t02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t02 OCA], [https://pdbe.org/5t02 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5t02 RCSB], [https://www.ebi.ac.uk/pdbsum/5t02 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5t02 ProSAT]</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=5t02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t02 OCA], [http://pdbe.org/5t02 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t02 RCSB], [http://www.ebi.ac.uk/pdbsum/5t02 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t02 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A0A0Y5D4F5_NEIME A0A0Y5D4F5_NEIME] |
| | <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 5t02" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5t02" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Thioesterase 3D structures|Thioesterase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Forwood, J K]] | + | [[Category: Large Structures]] |
| - | [[Category: Khandokar, Y B]] | + | [[Category: Neisseria meningitidis]] |
| - | [[Category: Srivastava, P]] | + | [[Category: Forwood JK]] |
| - | [[Category: Acyl-coa thioesterase]] | + | [[Category: Khandokar YB]] |
| - | [[Category: Coenzyme some]] | + | [[Category: Srivastava P]] |
| - | [[Category: Gdp]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Nisseria meningitidi]]
| + | |
| - | [[Category: Thioesterase]]
| + | |
| Structural highlights
Function
A0A0Y5D4F5_NEIME
Publication Abstract from PubMed
Thioesterases catalyze the cleavage of thioester bonds within many activated fatty acids and acyl-CoA substrates. They are expressed ubiquitously in both prokaryotes and eukaryotes and are subdivided into 25 thioesterase families according to their catalytic active site, protein oligomerization, and substrate specificity. While many of these enzyme families are well characterized in terms of function and substrate specificity, regulation across most thioesterase families is poorly understood. Here, we characterized a TE6 thioesterase from the bacterium Neisseria meningitidis. Structural analysis with X-ray crystallographic diffraction data to 2.0 A revealed that each protein subunit harbors a hot dog fold and that the TE6 enzyme forms a hexamer with D3 symmetry. An assessment of thioesterase activity against a range of acyl-CoA substrates revealed greatest activity against acetyl-CoA, and structure-guided mutagenesis of putative active site residues identified Asn-24 and Asp-39 as being essential for activity. Our structural analysis revealed that six GDP nucleotides bound the enzyme in close proximity to an intersubunit disulfide bond interactions that covalently link thioesterase domains in a double hot dog dimer. Structure-guided mutagenesis of residues within the GDP-binding pocket identified Arg-93 as playing a key role in the nucleotide interaction and revealed that GDP is required for activity. All mutations were confirmed to be specific and not to have resulted from structural perturbations by X-ray crystallography. This is the first report of a bacterial GDP-regulated thioesterase and of covalent linkage of thioesterase domains through a disulfide bond, revealing structural similarities with ADP regulation in the human ACOT12 thioesterase.
Structural insights into GDP-mediated regulation of a bacterial acyl-CoA thioesterase.,Khandokar YB, Srivastava P, Cowieson N, Sarker S, Aragao D, Das S, Smith KM, Raidal SR, Forwood JK J Biol Chem. 2017 Oct 2. pii: jbc.M117.800227. doi: 10.1074/jbc.M117.800227. PMID:28972175[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Khandokar YB, Srivastava P, Cowieson N, Sarker S, Aragao D, Das S, Smith KM, Raidal SR, Forwood JK. Structural insights into GDP-mediated regulation of a bacterial acyl-CoA thioesterase. J Biol Chem. 2017 Oct 2. pii: jbc.M117.800227. doi: 10.1074/jbc.M117.800227. PMID:28972175 doi:http://dx.doi.org/10.1074/jbc.M117.800227
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