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| | <StructureSection load='4zrb' size='340' side='right'caption='[[4zrb]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='4zrb' size='340' side='right'caption='[[4zrb]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4zrb]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Strpn Strpn]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZRB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZRB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4zrb]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_TIGR4 Streptococcus pneumoniae TIGR4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZRB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZRB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COA:COENZYME+A'>COA</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]] 2.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4i82|4i82]], [[4xy5|4xy5]], [[4xy6|4xy6]], [[4zrf|4zrf]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SP_1851 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=170187 STRPN])</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=4zrb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zrb OCA], [https://pdbe.org/4zrb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zrb RCSB], [https://www.ebi.ac.uk/pdbsum/4zrb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zrb 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=4zrb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zrb OCA], [http://pdbe.org/4zrb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zrb RCSB], [http://www.ebi.ac.uk/pdbsum/4zrb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zrb ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A0A0M3KL39_STRPN A0A0M3KL39_STRPN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Strpn]] | + | [[Category: Streptococcus pneumoniae TIGR4]] |
| - | [[Category: Forwood, J K]] | + | [[Category: Forwood JK]] |
| - | [[Category: Khandokar, Y B]] | + | [[Category: Khandokar YB]] |
| - | [[Category: Srivastava, P]] | + | [[Category: Srivastava P]] |
| - | [[Category: Hotdog fold]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Paai thioesterase]]
| + | |
| - | [[Category: Streptococcus pneumoniae]]
| + | |
| Structural highlights
Function
A0A0M3KL39_STRPN
Publication Abstract from PubMed
PaaI thioesterases are members of the TE13 thioesterase family which catalyse the hydrolysis of thioester bonds between coenzyme A and phenylacetyl-CoA. In this study we characterize the PaaI thioesterase from Streptococcus pneumoniae (SpPaaI), including structural analysis based on crystal diffraction data to 1.8 A resolution, to reveal two double hotdog domains arranged in a back-to-back configuration. Consistent with the crystallography data, both size exclusion chromatography and small angle X-ray scattering data support a tetrameric arrangement of thioesterase domains in solution. Assessment of SpPaaI activity against a range of acyl-CoA substrates showed activity for both phenylacetyl-CoA and medium-chain fatty-acyl CoA substrates. Mutagenesis of putative active site residues reveals Asn37, Asp52, and Thr68 are important for catalysis, and size exclusion chromatography analysis and X-ray crystallography confirm that these mutants retain the same tertiary and quaternary structures, establishing that the reduced activity is not a result of structural perturbations. Interestingly, the structure of SpPaaI in the presence of CoA provides a structural basis for the observed substrate specificity, accommodating a 10-carbon fatty acid chain, and a large conformational change of up to 38 A in the N-terminus, and a loop region involving Tyr38Tyr39. This is the first time PaaI thioesterases have displayed a dual specificity for medium-chain acyl-CoAs substrates and phenylacetyl-CoA substrates, and we provide a structural basis for this specificity, highlighting a novel induced fit mechanism that is likely to be conserved within members of this enzyme family.
Structural and Functional Characterization of the PaaI Thioesterase from Streptococcus pneumoniae Reveals a Dual Specificity for Phenylacetyl-CoA and Medium-Chain Fatty Acyl-CoAs and a Novel CoA Induced Fit Mechanism.,Khandokar YB, Srivastava P, Sarker S, Swarbrick CM, Aragao D, Cowieson N, Forwood JK J Biol Chem. 2015 Nov 4. pii: jbc.M115.677484. PMID:26538563[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Khandokar YB, Srivastava P, Sarker S, Swarbrick CM, Aragao D, Cowieson N, Forwood JK. Structural and Functional Characterization of the PaaI Thioesterase from Streptococcus pneumoniae Reveals a Dual Specificity for Phenylacetyl-CoA and Medium-Chain Fatty Acyl-CoAs and a Novel CoA Induced Fit Mechanism. J Biol Chem. 2015 Nov 4. pii: jbc.M115.677484. PMID:26538563 doi:http://dx.doi.org/10.1074/jbc.M115.677484
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