7aw5 - Revision history

OCA at 12:17, 1 February 2024

2024-02-01T12:17:20Z

←Older revision		Revision as of 12:17, 1 February 2024
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	==Crystal structure of OXA-48 beta-lactamase in the complex with the inhibitor ID3==		==Crystal structure of OXA-48 beta-lactamase in the complex with the inhibitor ID3==
-	<StructureSection load='7aw5' size='340' side='right'caption='[[7aw5]]' scene=''>	+	<StructureSection load='7aw5' size='340' side='right'caption='[[7aw5]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AW5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AW5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7aw5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AW5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AW5 FirstGlance]. <br>
-	</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=7aw5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aw5 OCA], [https://pdbe.org/7aw5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aw5 RCSB], [https://www.ebi.ac.uk/pdbsum/7aw5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aw5 ProSAT]</span></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]] 1.65Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=LKH:4-[(~{E})-[3-(4-chlorophenyl)-5-sulfanylidene-1~{H}-1,2,4-triazol-4-yl]iminomethyl]benzoic+acid'>LKH</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=7aw5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aw5 OCA], [https://pdbe.org/7aw5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aw5 RCSB], [https://www.ebi.ac.uk/pdbsum/7aw5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aw5 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q6XEC0_KLEPN Q6XEC0_KLEPN]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The major cause of bacterial resistance to beta-lactams is the production of hydrolytic beta-lactamase enzymes. Nowadays, the combination of beta-lactam antibiotics with beta-lactamase inhibitors (BLIs) is the main strategy for overcoming such issues. Nevertheless, particularly challenging beta-lactamases, such as OXA-48, pose the need for novel and effective treatments. Herein, we describe the screening of a proprietary compound collection against Klebsiella pneumoniae OXA-48, leading to the identification of several chemotypes, like the 4-ideneamino-4H-1,2,4-triazole (SC_2) and pyrazolo[3,4-b]pyridine (SC_7) cores as potential inhibitors. Importantly, the most potent representative of the latter series (ID2, AC50 = 0.99 muM) inhibited OXA-48 via a reversible and competitive mechanism of action, as demonstrated by biochemical and X-ray studies; furthermore, it slightly improved imipenem's activity in Escherichia coli ATCC BAA-2523 beta-lactam resistant strain. Also, ID2 showed good solubility and no sign of toxicity up to the highest tested concentration, resulting in a promising starting point for further optimization programs toward novel and effective non-beta-lactam BLIs.
		+
		+	Discovery of Novel Chemical Series of OXA-48 beta-Lactamase Inhibitors by High-Throughput Screening.,Garofalo B, Prati F, Buonfiglio R, Coletta I, D'Atanasio N, Molteni A, Carettoni D, Wanke V, Pochetti G, Montanari R, Capelli D, Milanese C, Di Giorgio FP, Ombrato R Pharmaceuticals (Basel). 2021 Jun 25;14(7). pii: ph14070612. doi:, 10.3390/ph14070612. PMID:34202402<ref>PMID:34202402</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7aw5" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta-lactamase 3D structures\|Beta-lactamase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Klebsiella pneumoniae]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Capelli D]]		[[Category: Capelli D]]

OCA at 08:56, 21 July 2021

2021-07-21T08:56:18Z

←Older revision		Revision as of 08:56, 21 July 2021
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-	'''Unreleased structure'''

-	~~The entry 7aw5 is ON HOLD until Paper Publication~~	+	==Crystal structure of OXA-48 beta-lactamase in the complex with the inhibitor ID3==
-		+	<StructureSection load='7aw5' size='340' side='right'caption='[[7aw5]]' scene=''>
-	~~Authors: Pochetti, G., Montanari, R., Capelli, D., Garofalo, B., Ombrato, R.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AW5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AW5 FirstGlance]. <br>
-	~~Description:~~ Crystal structure of OXA-48 beta-lactamase in the complex with the inhibitor ID3	+	</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=7aw5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aw5 OCA], [https://pdbe.org/7aw5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aw5 RCSB], [https://www.ebi.ac.uk/pdbsum/7aw5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aw5 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Ombrato, R~~]]	+	__TOC__
-	[[Category: ~~Pochetti, G~~]]	+	</StructureSection>
-	[[Category: Montanari, R]]	+	[[Category: Large Structures]]
-	[[Category: ~~Garofalo, B~~]]	+	[[Category: Capelli D]]
-	[[Category: ~~Capelli, D~~]]	+	[[Category: Garofalo B]]
		+	[[Category: Montanari R]]
		+	[[Category: Ombrato R]]
		+	[[Category: Pochetti G]]

OCA: Protected "7aw5" [edit=sysop:move=sysop]

2020-11-18T07:52:47Z

Protected "7aw5" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:52, 18 November 2020

OCA: New page: '''Unreleased structure''' The entry 7aw5 is ON HOLD until Paper Publication Authors: Pochetti, G., Montanari, R., Capelli, D., Garofalo, B., Ombrato, R. Description: Crystal structure...

2020-11-18T07:52:46Z

New page: '''Unreleased structure''' The entry 7aw5 is ON HOLD until Paper Publication Authors: Pochetti, G., Montanari, R., Capelli, D., Garofalo, B., Ombrato, R. Description: Crystal structure...

New page

'''Unreleased structure'''

The entry 7aw5 is ON HOLD until Paper Publication

Authors: Pochetti, G., Montanari, R., Capelli, D., Garofalo, B., Ombrato, R.

Description: Crystal structure of OXA-48 beta-lactamase in the complex with the inhibitor ID3
[[Category: Unreleased Structures]]
[[Category: Ombrato, R]]
[[Category: Pochetti, G]]
[[Category: Montanari, R]]
[[Category: Garofalo, B]]
[[Category: Capelli, D]]