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4cl6

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Revision as of 07:20, 14 September 2022

Crystal Structure of 3-hydroxydecanoyl-Acyl Carrier Protein Dehydratase (FabA) from Pseudomonas aeruginosa in complex with N-(4- Chlorobenzyl)-3-(2-furyl)-1H-1,2,4-triazol-5-amine

Structural highlights

4cl6 is a 5 chain structure with sequence from Pseudomonas aeruginosa PAO1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[FABA_PSEAE] Necessary for the introduction of cis unsaturation into fatty acids. Catalyzes the dehydration of (3R)-3-hydroxydecanoyl-ACP to E-(2)-decenoyl-ACP and then its isomerization to Z-(3)-decenoyl-ACP. Can catalyze the dehydratase reaction for beta-hydroxyacyl-ACPs with saturated chain lengths up to 16:0, being most active on intermediate chain length (By similarity).

Publication Abstract from PubMed

Eukaryotes and prokaryotes possess fatty acid synthase (FAS) biosynthetic pathways that comprise iterative chain elongation, reduction, and dehydration reactions. The bacterial FASII pathway differs significantly from human FAS pathways and is a long-standing target for antibiotic development against Gram-negative bacteria due to differences from the human FAS, and several existing antibacterial agents are known to inhibit FASII enzymes. N-Acetylcysteamine (NAC) fatty acid thioesters have been used as mimics of the natural acyl carrier protein pathway intermediates to assay FASII enzymes, and we now report an assay of FabV from Pseudomonas aeruginosa using (E)-2-decenoyl-NAC. In addition, we have converted an existing UV absorbance assay for FabA, the bifunctional dehydration/epimerization enzyme and key target in the FASII pathway, into a high-throughput enzyme coupled fluorescence assay that has been employed to screen a library of diverse small molecules. With this approach, N-(4-chlorobenzyl)-3-(2-furyl)-1H-1,2,4-triazol-5-amine (N42FTA) was found to competitively inhibit (pIC50=5.7+/-0.2) the processing of 3-hydroxydecanoyl-NAC by P. aeruginosa FabA. N42FTA was shown to be potent in blocking crosslinking of Escherichiacoli acyl carrier protein and FabA, a direct mimic of the biological process. The co-complex structure of N42FTA with P. aeruginosa FabA protein rationalises affinity and suggests future design opportunities. Employing NAC fatty acid mimics to develop further high-throughput assays for individual enzymes in the FASII pathway should aid in the discovery of new antimicrobials.

A Substrate Mimic Allows High-Throughput Assay of the FabA Protein and Consequently the Identification of a Novel Inhibitor of Pseudomonas aeruginosa FabA.,Moynie L, Hope AG, Finzel K, Schmidberger J, Leckie SM, Schneider G, Burkart MD, Smith AD, Gray DW, Naismith JH J Mol Biol. 2015 Nov 10. pii: S0022-2836(15)00621-X. doi:, 10.1016/j.jmb.2015.10.027. PMID:26562505^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Moynie L, Hope AG, Finzel K, Schmidberger J, Leckie SM, Schneider G, Burkart MD, Smith AD, Gray DW, Naismith JH. A Substrate Mimic Allows High-Throughput Assay of the FabA Protein and Consequently the Identification of a Novel Inhibitor of Pseudomonas aeruginosa FabA. J Mol Biol. 2015 Nov 10. pii: S0022-2836(15)00621-X. doi:, 10.1016/j.jmb.2015.10.027. PMID:26562505 doi:http://dx.doi.org/10.1016/j.jmb.2015.10.027

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4cl6"

@@ Line 3: / Line 3: @@
 <StructureSection load='4cl6' size='340' side='right'caption='[[4cl6]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4cl6]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Pseae Pseae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CL6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CL6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4cl6]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CL6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CL6 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7SB:N-(4-CHLOROBENZYL)-5-(FURAN-2-YL)-1H-1,2,4-TRIAZOL-3-AMINE'>7SB</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7SB:N-(4-CHLOROBENZYL)-5-(FURAN-2-YL)-1H-1,2,4-TRIAZOL-3-AMINE'>7SB</scene></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=4cl6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cl6 OCA], [http://pdbe.org/4cl6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cl6 RCSB], [http://www.ebi.ac.uk/pdbsum/4cl6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cl6 ProSAT]</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=4cl6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cl6 OCA], [https://pdbe.org/4cl6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cl6 RCSB], [https://www.ebi.ac.uk/pdbsum/4cl6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cl6 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/FABA_PSEAE FABA_PSEAE]] Necessary for the introduction of cis unsaturation into fatty acids. Catalyzes the dehydration of (3R)-3-hydroxydecanoyl-ACP to E-(2)-decenoyl-ACP and then its isomerization to Z-(3)-decenoyl-ACP. Can catalyze the dehydratase reaction for beta-hydroxyacyl-ACPs with saturated chain lengths up to 16:0, being most active on intermediate chain length (By similarity).
+[[https://www.uniprot.org/uniprot/FABA_PSEAE FABA_PSEAE]] Necessary for the introduction of cis unsaturation into fatty acids. Catalyzes the dehydration of (3R)-3-hydroxydecanoyl-ACP to E-(2)-decenoyl-ACP and then its isomerization to Z-(3)-decenoyl-ACP. Can catalyze the dehydratase reaction for beta-hydroxyacyl-ACPs with saturated chain lengths up to 16:0, being most active on intermediate chain length (By similarity).
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 26: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Pseae]]
+[[Category: Pseudomonas aeruginosa PAO1]]
-[[Category: Duthie, F G]]
+[[Category: Duthie FG]]
-[[Category: McMahon, S A]]
+[[Category: McMahon SA]]
-[[Category: Moynie, L]]
+[[Category: Moynie L]]
-[[Category: Naismith, J H]]
+[[Category: Naismith JH]]
-[[Category: Bacterial virulence]]
-[[Category: Drug discovery]]
-[[Category: Fatty acid biosynthesis]]
-[[Category: Lyase]]

4cl6

From Proteopedia

Revision as of 07:20, 14 September 2022

Crystal Structure of 3-hydroxydecanoyl-Acyl Carrier Protein Dehydratase (FabA) from Pseudomonas aeruginosa in complex with N-(4- Chlorobenzyl)-3-(2-furyl)-1H-1,2,4-triazol-5-amine

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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