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| | ==Crystal structure of 3-ketoacyl-(acyl-carrier-protein) reductase (FabG)(G92D) from Vibrio cholerae== | | ==Crystal structure of 3-ketoacyl-(acyl-carrier-protein) reductase (FabG)(G92D) from Vibrio cholerae== |
| - | <StructureSection load='3u09' size='340' side='right' caption='[[3u09]], [[Resolution|resolution]] 1.75Å' scene=''> | + | <StructureSection load='3u09' size='340' side='right'caption='[[3u09]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3u09]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Vibch Vibch]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U09 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3U09 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3u09]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_cholerae_O1_biovar_El_Tor_str._N16961 Vibrio cholerae O1 biovar El Tor str. N16961]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U09 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U09 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</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]] 1.75Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fabG, VC2021, VC_2021 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243277 VIBCH])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3-oxoacyl-[acyl-carrier-protein]_reductase 3-oxoacyl-[acyl-carrier-protein] reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.100 1.1.1.100] </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=3u09 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u09 OCA], [https://pdbe.org/3u09 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u09 RCSB], [https://www.ebi.ac.uk/pdbsum/3u09 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u09 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=3u09 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u09 OCA], [http://pdbe.org/3u09 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3u09 RCSB], [http://www.ebi.ac.uk/pdbsum/3u09 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3u09 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FABG_VIBCH FABG_VIBCH]] Catalyzes the NADPH-dependent reduction of beta-ketoacyl-ACP substrates to beta-hydroxyacyl-ACP products, the first reductive step in the elongation cycle of fatty acid biosynthesis. | + | [https://www.uniprot.org/uniprot/FABG_VIBCH FABG_VIBCH] Catalyzes the NADPH-dependent reduction of beta-ketoacyl-ACP substrates to beta-hydroxyacyl-ACP products, the first reductive step in the elongation cycle of fatty acid biosynthesis. |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | beta-ketoacyl-(acyl carrier protein) reductase (FabG) catalyzes the key reductive reaction in the elongation cycle of fatty acid synthesis (FAS), which is a vital metabolic pathway in bacteria and a promising target for new antibiotic development. The activation of the enzyme is usually linked to the formation of a catalytic triad and cofactor binding, and crystal structures of FabG from different organisms have been captured in either active or inactive conformations. However, the structural elements which enable activation of FabG require further exploration. Here we report structural, enzymatic, and binding studies of vcFabG, the FabG protein found in the causative agent of cholera, Vibrio cholerae. vcFabG exists predominantly as a dimer in solution and is able to self-associate to form tetramers, which is the state seen in the crystal structure. The formation of the tetramer may be promoted by the presence of the cofactor NADP(H). The transition between dimeric and tetrameric states of vcFabG is related to changes in the conformations of the alpha4/alpha5 helices on the dimer-dimer interface. Two glycine residues adjacent to the dimer interface (G92 and G141) are identified as the hinge for the conformational changes, while the catalytic tyrosine (Y155) and a glutamine residue that forms hydrogen bonds to both loops beta4-alpha4 and beta5-alpha5 (Q152) stabilize the active conformation. The functions of the aforementioned residues were confirmed by the binding and enzymatic assays for the corresponding mutants. IMPORTANCE: This paper describes structural, enzymatic, and binding studies of FabG from Vibrio cholera. In this work we dissect the structural elements responsible for the activation of vcFabG. The structural information provided here is essential for the development of antibiotics specifically targeting bacteria FabG, especially for the multi-drug resistant strains of V. cholerae.
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| - | Dissecting the structural elements for the activation of beta-ketoacyl-(acyl carrier protein) reductase from Vibrio cholerae.,Hou J, Zheng H, Chruszcz M, Zimmerman MD, Shumilin IA, Osinski T, Demas M, Grimshaw S, Minor W J Bacteriol. 2015 Nov 9. pii: JB.00360-15. PMID:26553852<ref>PMID:26553852</ref>
| + | ==See Also== |
| - | | + | *[[Beta-hydroxyacyl-acyl carrier protein dehydratase 3D structures|Beta-hydroxyacyl-acyl carrier protein dehydratase 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | *[[Beta-ketoacyl carrier protein reductase 3D structures|Beta-ketoacyl carrier protein reductase 3D structures]] |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3u09" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Vibch]] | + | [[Category: Large Structures]] |
| - | [[Category: Anderson, W F]] | + | [[Category: Vibrio cholerae O1 biovar El Tor str. N16961]] |
| - | [[Category: Structural genomic]] | + | [[Category: Anderson WF]] |
| - | [[Category: Chruszcz, M]] | + | [[Category: Chruszcz M]] |
| - | [[Category: Fratczak, Z]] | + | [[Category: Fratczak Z]] |
| - | [[Category: Grabowski, M]] | + | [[Category: Grabowski M]] |
| - | [[Category: Hou, J]] | + | [[Category: Hou J]] |
| - | [[Category: Minor, W]] | + | [[Category: Minor W]] |
| - | [[Category: Zheng, H]] | + | [[Category: Zheng H]] |
| - | [[Category: Csgid]]
| + | |
| - | [[Category: Fabg]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Vibrio cholerae]]
| + | |
