6zxi - Revision history

OCA at 07:51, 7 February 2024

OCA — Wed, 07 Feb 2024 07:51:07 GMT

←Older revision		Revision as of 07:51, 7 February 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6zxi]] 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=6ZXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZXI FirstGlance]. <br>		<table><tr><td colspan='2'>[[6zxi]] 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=6ZXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZXI FirstGlance]. <br>
-	</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=CO2:CARBON+DIOXIDE'>CO2</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=QS8:[[(3~{R},6~{R})-6-fluoranyl-1-methanoyl-piperidin-3-yl]amino]+hydrogen+sulfate'>QS8</scene></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]] 1.85Å</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=CO2:CARBON+DIOXIDE'>CO2</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=QS8:[[(3~{R},6~{R})-6-fluoranyl-1-methanoyl-piperidin-3-yl]amino]+hydrogen+sulfate'>QS8</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=6zxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zxi OCA], [https://pdbe.org/6zxi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zxi RCSB], [https://www.ebi.ac.uk/pdbsum/6zxi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zxi 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=6zxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zxi OCA], [https://pdbe.org/6zxi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zxi RCSB], [https://www.ebi.ac.uk/pdbsum/6zxi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zxi ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/Q6XEC0_KLEPN Q6XEC0_KLEPN]		[https://www.uniprot.org/uniprot/Q6XEC0_KLEPN Q6XEC0_KLEPN]
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The diazabicyclooctanes (DBOs) are a class of serine beta-lactamase (SBL) inhibitors that use a strained urea moiety as the warhead to react with the active serine residue in the active site of SBLs. The first in-class drug, avibactam, as well as several other recently approved DBOs (e.g., relebactam) or those in clinical development (e.g., nacubactam and zidebactam) potentiate activity of beta-lactam antibiotics, to various extents, against carbapenem-resistant Enterobacterales (CRE) carrying class A, C, and D SBLs; however, none of these are able to rescue the activity of beta-lactam antibiotics against carbapenem-resistant Acinetobacter baumannii (CRAB), a WHO "critical priority pathogen" producing class D OXA-type SBLs. Herein, we describe the chemical optimization and resulting structure-activity relationship, leading to the discovery of a novel DBO, ANT3310, which uniquely has a fluorine atom replacing the carboxamide and stands apart from the current DBOs in restoring carbapenem activity against OXA-CRAB as well as SBL-carrying CRE pathogens.
-
-	Discovery of ANT3310, a Novel Broad-Spectrum Serine beta-Lactamase Inhibitor of the Diazabicyclooctane Class, Which Strongly Potentiates Meropenem Activity against Carbapenem-Resistant Enterobacterales and Acinetobacter baumannii.,Davies DT, Leiris S, Zalacain M, Sprynski N, Castandet J, Bousquet J, Lozano C, Llanos A, Alibaud L, Vasa S, Pattipati R, Valige R, Kummari B, Pothukanuri S, De Piano C, Morrissey I, Holden K, Warn P, Marcoccia F, Benvenuti M, Pozzi C, Tassone G, Mangani S, Docquier JD, Pallin D, Elliot R, Lemonnier M, Everett M J Med Chem. 2020 Dec 24;63(24):15802-15820. doi: 10.1021/acs.jmedchem.0c01535. , Epub 2020 Dec 11. PMID:33306385<ref>PMID:33306385</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 6zxi" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 06:09, 2 March 2023

OCA — Thu, 02 Mar 2023 06:09:32 GMT

←Older revision		Revision as of 06:09, 2 March 2023
Line 1:		Line 1:

	==Crystal Structure of the OXA-48 Carbapenem-Hydrolyzing Class D beta-Lactamase in Complex with the DBO inhibitor ANT3310==		==Crystal Structure of the OXA-48 Carbapenem-Hydrolyzing Class D beta-Lactamase in Complex with the DBO inhibitor ANT3310==
-	<StructureSection load='6zxi' size='340' side='right'caption='[[6zxi]]' scene=''>	+	<StructureSection load='6zxi' size='340' side='right'caption='[[6zxi]], [[Resolution\|resolution]] 1.85Å' 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=6ZXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZXI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6zxi]] 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=6ZXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZXI 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=6zxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zxi OCA], [https://pdbe.org/6zxi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zxi RCSB], [https://www.ebi.ac.uk/pdbsum/6zxi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zxi ProSAT]</span></td></tr>	+	</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=CO2:CARBON+DIOXIDE'>CO2</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=QS8:[[(3~{R},6~{R})-6-fluoranyl-1-methanoyl-piperidin-3-yl]amino]+hydrogen+sulfate'>QS8</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=6zxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zxi OCA], [https://pdbe.org/6zxi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zxi RCSB], [https://www.ebi.ac.uk/pdbsum/6zxi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zxi 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 diazabicyclooctanes (DBOs) are a class of serine beta-lactamase (SBL) inhibitors that use a strained urea moiety as the warhead to react with the active serine residue in the active site of SBLs. The first in-class drug, avibactam, as well as several other recently approved DBOs (e.g., relebactam) or those in clinical development (e.g., nacubactam and zidebactam) potentiate activity of beta-lactam antibiotics, to various extents, against carbapenem-resistant Enterobacterales (CRE) carrying class A, C, and D SBLs; however, none of these are able to rescue the activity of beta-lactam antibiotics against carbapenem-resistant Acinetobacter baumannii (CRAB), a WHO "critical priority pathogen" producing class D OXA-type SBLs. Herein, we describe the chemical optimization and resulting structure-activity relationship, leading to the discovery of a novel DBO, ANT3310, which uniquely has a fluorine atom replacing the carboxamide and stands apart from the current DBOs in restoring carbapenem activity against OXA-CRAB as well as SBL-carrying CRE pathogens.
		+
		+	Discovery of ANT3310, a Novel Broad-Spectrum Serine beta-Lactamase Inhibitor of the Diazabicyclooctane Class, Which Strongly Potentiates Meropenem Activity against Carbapenem-Resistant Enterobacterales and Acinetobacter baumannii.,Davies DT, Leiris S, Zalacain M, Sprynski N, Castandet J, Bousquet J, Lozano C, Llanos A, Alibaud L, Vasa S, Pattipati R, Valige R, Kummari B, Pothukanuri S, De Piano C, Morrissey I, Holden K, Warn P, Marcoccia F, Benvenuti M, Pozzi C, Tassone G, Mangani S, Docquier JD, Pallin D, Elliot R, Lemonnier M, Everett M J Med Chem. 2020 Dec 24;63(24):15802-15820. doi: 10.1021/acs.jmedchem.0c01535. , Epub 2020 Dec 11. PMID:33306385<ref>PMID:33306385</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6zxi" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Klebsiella pneumoniae]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Benvenuti M]]		[[Category: Benvenuti M]]

OCA at 06:05, 11 August 2021

OCA — Wed, 11 Aug 2021 06:05:01 GMT

←Older revision		Revision as of 06:05, 11 August 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6zxi is ~~ON HOLD until Paper Publication~~	+	==Crystal Structure of the OXA-48 Carbapenem-Hydrolyzing Class D beta-Lactamase in Complex with the DBO inhibitor ANT3310==
-		+	<StructureSection load='6zxi' size='340' side='right'caption='[[6zxi]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZXI FirstGlance]. <br>
-	~~Description~~:	+	</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=6zxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zxi OCA], [https://pdbe.org/6zxi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zxi RCSB], [https://www.ebi.ac.uk/pdbsum/6zxi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zxi ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Benvenuti M]]
		+	[[Category: De Luca F]]
		+	[[Category: Docquier JD]]
		+	[[Category: Mangani S]]
		+	[[Category: Pozzi C]]

OCA at 04:58, 2 September 2020

OCA — Wed, 02 Sep 2020 04:58:30 GMT

←Older revision		Revision as of 04:58, 2 September 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6zxi is ON HOLD	+	The entry 6zxi is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6zxi" [edit=sysop:move=sysop]

OCA — Wed, 05 Aug 2020 04:03:31 GMT

Protected "6zxi" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:03, 5 August 2020

OCA: New page: '''Unreleased structure''' The entry 6zxi is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 05 Aug 2020 04:03:30 GMT

New page: '''Unreleased structure''' The entry 6zxi is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6zxi is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]