3rsh: Difference between revisions
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<StructureSection load='3rsh' size='340' side='right' caption='[[3rsh]], [[Resolution|resolution]] 1.95Å' scene=''> | <StructureSection load='3rsh' size='340' side='right' caption='[[3rsh]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3rsh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3rsh]] 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=3RSH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RSH FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3op4|3op4]], [[3rro|3rro]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3op4|3op4]], [[3rro|3rro]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VCD_002346 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id= | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VCD_002346 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243277 VIBCH])</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='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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3rsh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rsh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rsh RCSB], [http://www.ebi.ac.uk/pdbsum/3rsh PDBsum]</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=3rsh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rsh OCA], [http://pdbe.org/3rsh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3rsh RCSB], [http://www.ebi.ac.uk/pdbsum/3rsh PDBsum]</span></td></tr> | ||
</table> | </table> | ||
<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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3rsh" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Beta-ketoacyl-ACP reductase|Beta-ketoacyl-ACP reductase]] | *[[Beta-ketoacyl-ACP reductase|Beta-ketoacyl-ACP reductase]] | ||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Vibch]] | ||
[[Category: Anderson, W]] | [[Category: Anderson, W]] | ||
[[Category: Structural genomic]] | [[Category: Structural genomic]] | ||
Revision as of 00:29, 1 December 2015
Structure of 3-ketoacyl-(acyl-carrier-protein)reductase (FabG) from Vibrio cholerae O1 complexed with NADP+ (space group P62)Structure of 3-ketoacyl-(acyl-carrier-protein)reductase (FabG) from Vibrio cholerae O1 complexed with NADP+ (space group P62)
Structural highlights
Publication Abstract from PubMedbeta-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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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