8z5c: Difference between revisions
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==Cystal structure of beta-ketoacyl-ACP synthase FabF from Helicobacter pylori== | |||
<StructureSection load='8z5c' size='340' side='right'caption='[[8z5c]], [[Resolution|resolution]] 1.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8z5c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori Helicobacter pylori]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8Z5C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8Z5C 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=RB:RUBIDIUM+ION'>RB</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=8z5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8z5c OCA], [https://pdbe.org/8z5c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8z5c RCSB], [https://www.ebi.ac.uk/pdbsum/8z5c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8z5c ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A438WLJ1_HELPX A0A438WLJ1_HELPX] Involved in the type II fatty acid elongation cycle. Catalyzes the elongation of a wide range of acyl-ACP by the addition of two carbons from malonyl-ACP to an acyl acceptor. Can efficiently catalyze the conversion of palmitoleoyl-ACP (cis-hexadec-9-enoyl-ACP) to cis-vaccenoyl-ACP (cis-octadec-11-enoyl-ACP), an essential step in the thermal regulation of fatty acid composition.[PIRNR:PIRNR000447] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Fatty acids produced by the type-II fatty acid biosynthesis pathway (FAS-II) are essential biomaterials for bacterial membrane construction and numerous metabolic routes. The beta-ketoacyl-ACP synthase FabF catalyzes the key C-C bond formation step for fatty acid extension in FAS-II. Here, we revealed the substrate recognition and catalytic mechanisms of FabF by determining FabF-ACP complexes. FabF displays a distinctive bimodal catalytic pattern specifically on C6 and C10 acyl-ACP substrates. It utilizes positively charged residues located on the eta3-helix and loop1 regions near the catalytic tunnel entrance to bind ACP, and two hydrophobic cavities as well as "front", "middle", and "back" door residues to specifically stabilize C6 and C10 acyl substrates for preferential catalysis. Further quantum chemistry calculations suggest that the FabF catalytic residues Lys336 and His304 facilitate proton transfer during condensation catalysis and C-C bond formation. Our results provide key mechanistic insights into the biosynthesis of molecular carbon skeletons based on ketosynthases that are highly conserved through the FAS and polyketide synthase (PKS) analogous biosynthetic routes, broaden the understanding of the tricarboxylic acid cycle that utilizes lipoic acid derived from C8-ACP accumulated due to the FabF distinctive catalytic pattern for oxidative decarboxylations, and may facilitate the development of narrow-spectrum antibacterial drugs. | |||
The beta-Ketoacyl-ACP Synthase FabF Catalyzes Carbon-Carbon Bond Formation in a Bimodal Pattern for Fatty Acid Biosynthesis.,Zhang L, Huang Y, Wang Y, Cai C, Zhang L, Ye F Angew Chem Int Ed Engl. 2024 Aug 22:e202407921. doi: 10.1002/anie.202407921. PMID:39175097<ref>PMID:39175097</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Huang | <div class="pdbe-citations 8z5c" style="background-color:#fffaf0;"></div> | ||
[[Category: Zhang | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Helicobacter pylori]] | |||
[[Category: Large Structures]] | |||
[[Category: Huang YZ]] | |||
[[Category: Zhang L]] | |||
Latest revision as of 10:05, 9 October 2024
Cystal structure of beta-ketoacyl-ACP synthase FabF from Helicobacter pyloriCystal structure of beta-ketoacyl-ACP synthase FabF from Helicobacter pylori
Structural highlights
FunctionA0A438WLJ1_HELPX Involved in the type II fatty acid elongation cycle. Catalyzes the elongation of a wide range of acyl-ACP by the addition of two carbons from malonyl-ACP to an acyl acceptor. Can efficiently catalyze the conversion of palmitoleoyl-ACP (cis-hexadec-9-enoyl-ACP) to cis-vaccenoyl-ACP (cis-octadec-11-enoyl-ACP), an essential step in the thermal regulation of fatty acid composition.[PIRNR:PIRNR000447] Publication Abstract from PubMedFatty acids produced by the type-II fatty acid biosynthesis pathway (FAS-II) are essential biomaterials for bacterial membrane construction and numerous metabolic routes. The beta-ketoacyl-ACP synthase FabF catalyzes the key C-C bond formation step for fatty acid extension in FAS-II. Here, we revealed the substrate recognition and catalytic mechanisms of FabF by determining FabF-ACP complexes. FabF displays a distinctive bimodal catalytic pattern specifically on C6 and C10 acyl-ACP substrates. It utilizes positively charged residues located on the eta3-helix and loop1 regions near the catalytic tunnel entrance to bind ACP, and two hydrophobic cavities as well as "front", "middle", and "back" door residues to specifically stabilize C6 and C10 acyl substrates for preferential catalysis. Further quantum chemistry calculations suggest that the FabF catalytic residues Lys336 and His304 facilitate proton transfer during condensation catalysis and C-C bond formation. Our results provide key mechanistic insights into the biosynthesis of molecular carbon skeletons based on ketosynthases that are highly conserved through the FAS and polyketide synthase (PKS) analogous biosynthetic routes, broaden the understanding of the tricarboxylic acid cycle that utilizes lipoic acid derived from C8-ACP accumulated due to the FabF distinctive catalytic pattern for oxidative decarboxylations, and may facilitate the development of narrow-spectrum antibacterial drugs. The beta-Ketoacyl-ACP Synthase FabF Catalyzes Carbon-Carbon Bond Formation in a Bimodal Pattern for Fatty Acid Biosynthesis.,Zhang L, Huang Y, Wang Y, Cai C, Zhang L, Ye F Angew Chem Int Ed Engl. 2024 Aug 22:e202407921. doi: 10.1002/anie.202407921. PMID:39175097[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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