5sof - Revision history

OCA at 18:19, 7 May 2025

2025-05-07T18:19:51Z

← Older revision		Revision as of 18:19, 7 May 2025
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	<table><tr><td colspan='2'>[[5sof]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SOF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SOF FirstGlance]. <br>		<table><tr><td colspan='2'>[[5sof]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SOF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SOF 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]] 1.5Å</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]] 1.5Å</td></tr>
	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NUA:N-(1-~~ethyl-1H-pyrazol~~-4-yl)cyclobutanecarboxamide'>NUA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NUA:~{N}-(1-ethylpyrazol-4-yl)cyclobutanecarboxamide'>NUA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=5sof FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sof OCA], [https://pdbe.org/5sof PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5sof RCSB], [https://www.ebi.ac.uk/pdbsum/5sof PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5sof 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=5sof FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sof OCA], [https://pdbe.org/5sof PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5sof RCSB], [https://www.ebi.ac.uk/pdbsum/5sof PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5sof ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/~~O54440_PSEAI O54440_PSEAI~~] Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP (By similarity).[PIRNR:PIRNR000447]		[https://www.uniprot.org/uniprot/G3XDA2_PSEAE G3XDA2_PSEAE] Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP (By similarity).[PIRNR:PIRNR000447]
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			There is an urgent need for new antibiotics. FabF (3-oxoacyl-[acyl-carrier-protein] synthase 2), which catalyses the rate limiting condensation reaction in the fatty acid synthesis II pathway, is an attractive target. Very few inhibitors of FabF are known and most are derived from natural products. In an effort to further explore the chemical space of FabF ligands, we have carried out fragment screening by X-ray crystallography against an intermediated state-mimicking variant of P. aeruginosa FabF (PaFabF C164Q). This screen has resulted in 48 hits out of which 16 bind in or close to the malonyl-CoA or fatty acid binding site or an adjacent dimer interface. None of the closer investigated fragments were active in a binding assay, but the same was the case for fragments derived from a potent FabF inhibitor. For hit optimization, we focused on the two fragments binding close to the catalytic residues of FabF. Different strategies were followed in the optimization process: exploration of commercially available analogues, fragment merging, virtual screening of a combinatorial make-on-demand space, and design and in-house synthesis of analogues. In total, more than 90 analogues of the hit compounds were explored, and for 10 of those co-crystal structures could be determined. The most potent ligand was discovered using manual structure-based design and has a binding affinity of 65 muM. This data package forms a strong foundation for the development of more potent and diverse FabF inhibitors.

			Towards new antibiotics: P. aeruginosa FabF ligands discovered by crystallographic fragment screening followed by hit expansion.,Georgiou C, Espeland LO, Bukya H, Yadrykhins'ky V, Haug BE, Mainkar PS, Brenk R Eur J Med Chem. 2025 Apr 3;291:117563. doi: 10.1016/j.ejmech.2025.117563. PMID:40233425<ref>PMID:40233425</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 5sof" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 09:58, 20 December 2023

2023-12-20T09:58:47Z

← Older revision		Revision as of 09:58, 20 December 2023
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	~~'''Unreleased structure'''~~

	~~The entry 5sof is ON HOLD until Paper Publication~~		==PanDDA analysis group deposition -- Crystal Structure of Pseudomonas Aeruginosa FabF-C164Q mutant protein in complex with Z373768900==
			<StructureSection load='5sof' size='340' side='right'caption='[[5sof]], [[Resolution\|resolution]] 1.50Å' scene=''>
	~~Authors: Brenk, R., Georgiou, C.~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[5sof]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SOF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SOF FirstGlance]. <br>
	~~Description:~~ PanDDA analysis group deposition --Crystal Structure of Pseudomonas Aeruginosa FabF-C164Q mutant protein in complex with Z373768900		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.5Å</td></tr>
	[[Category: ~~Unreleased~~ Structures]]		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NUA:N-(1-ethyl-1H-pyrazol-4-yl)cyclobutanecarboxamide'>NUA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
	[[Category: Brenk, R]]		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5sof FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sof OCA], [https://pdbe.org/5sof PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5sof RCSB], [https://www.ebi.ac.uk/pdbsum/5sof PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5sof ProSAT]</span></td></tr>
	[[Category: Georgiou, C]]		</table>
			== Function ==
			[https://www.uniprot.org/uniprot/O54440_PSEAI O54440_PSEAI] Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP (By similarity).[PIRNR:PIRNR000447]
			__TOC__
			</StructureSection>
			[[Category: Large Structures]]
			[[Category: Pseudomonas aeruginosa]]
			[[Category: Brenk R]]
			[[Category: Georgiou C]]

OCA at 06:03, 22 June 2022

2022-06-22T06:03:19Z

← Older revision		Revision as of 06:03, 22 June 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 5sof is ON HOLD		The entry 5sof is ON HOLD until Paper Publication

	Authors: Brenk, R., Georgiou, C.		Authors: Brenk, R., Georgiou, C.

OCA: Protected "5sof" [edit=sysop:move=sysop]

2022-06-08T03:46:27Z

Protected "5sof" [edit=sysop:move=sysop]

← Older revision	Revision as of 03:46, 8 June 2022
(No difference)

OCA: New page: '''Unreleased structure''' The entry 5sof is ON HOLD Authors: Brenk, R., Georgiou, C. Description: PanDDA analysis group deposition --Crystal Structure of Pseudomonas Aeruginosa FabF-C...

2022-06-08T03:46:26Z

New page: '''Unreleased structure''' The entry 5sof is ON HOLD Authors: Brenk, R., Georgiou, C. Description: PanDDA analysis group deposition --Crystal Structure of Pseudomonas Aeruginosa FabF-C...

New page

'''Unreleased structure'''

The entry 5sof is ON HOLD

Authors: Brenk, R., Georgiou, C.

Description: PanDDA analysis group deposition --Crystal Structure of Pseudomonas Aeruginosa FabF-C164Q mutant protein in complex with Z373768900
[[Category: Unreleased Structures]]
[[Category: Brenk, R]]
[[Category: Georgiou, C]]