6b1y - Revision history

OCA at 21:35, 28 October 2020

2020-10-28T21:35:35Z

←Older revision		Revision as of 21:35, 28 October 2020
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	==Crystal structure KPC-2 beta-lactamase complexed with WCK 5153 by co-crystallization==		==Crystal structure KPC-2 beta-lactamase complexed with WCK 5153 by co-crystallization==
-	<StructureSection load='6b1y' size='340' side='right' caption='[[6b1y]], [[Resolution\|resolution]] 1.80Å' scene=''>	+	<StructureSection load='6b1y' size='340' side='right'caption='[[6b1y]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6b1y]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B1Y OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6B1Y FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6b1y]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B1Y OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6B1Y FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD7:(2S,5Z)-1-formyl-5-imino-N-[(3R)-1-(sulfooxy)pyrrolidine-3-carbonyl]piperidine-2-carbohydrazide'>CD7</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD7:(2S,5Z)-1-formyl-5-imino-N-[(3R)-1-(sulfooxy)pyrrolidine-3-carbonyl]piperidine-2-carbohydrazide'>CD7</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6b1x\|6b1x]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6b1x\|6b1x]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></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=6b1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b1y OCA], [http://pdbe.org/6b1y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b1y RCSB], [http://www.ebi.ac.uk/pdbsum/6b1y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b1y ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6b1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b1y OCA], [http://pdbe.org/6b1y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b1y RCSB], [http://www.ebi.ac.uk/pdbsum/6b1y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b1y ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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	</div>		</div>
	<div class="pdbe-citations 6b1y" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6b1y" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta-lactamase 3D structures\|Beta-lactamase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Beta-lactamase]]		[[Category: Beta-lactamase]]
		+	[[Category: Large Structures]]
	[[Category: Akker, F van den]]		[[Category: Akker, F van den]]
	[[Category: Nguyen, N Q]]		[[Category: Nguyen, N Q]]

OCA at 18:43, 1 August 2018

2018-08-01T18:43:12Z

←Older revision		Revision as of 18:43, 1 August 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 6b1y is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure KPC-2 beta-lactamase complexed with WCK 5153 by co-crystallization==
		+	<StructureSection load='6b1y' size='340' side='right' caption='[[6b1y]], [[Resolution\|resolution]] 1.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6b1y]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B1Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B1Y FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD7:(2S,5Z)-1-formyl-5-imino-N-[(3R)-1-(sulfooxy)pyrrolidine-3-carbonyl]piperidine-2-carbohydrazide'>CD7</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6b1x\|6b1x]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></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=6b1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b1y OCA], [http://pdbe.org/6b1y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b1y RCSB], [http://www.ebi.ac.uk/pdbsum/6b1y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b1y ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/BLKPC_KLEPN BLKPC_KLEPN]] Hydrolyzes carbapenems, penicillins, cephalosporins and monobactams with varying efficiency.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Limited treatment options exist to combat infections caused by multidrug-resistant (MDR) Gram-negative bacteria possessing broad-spectrum beta-lactamases. The design of novel beta-lactamase inhibitors is of paramount importance. Here, three novel diazabicyclooctanes (DBOs), WCK 5153, zidebactam (WCK 5107), and WCK 4234 (compounds 1-3, respectively), were synthesized and biochemically characterized against clinically important bacteria. Compound 3 inhibited class A, C, and D beta-lactamases with unprecedented k2/ K values against OXA carbapenemases. Compounds 1 and 2 acylated class A and C beta-lactamses rapidly but not the tested OXAs. Compounds 1-3 formed highly stable acyl-complexes as demonstrated by mass spectrometry. Crystallography revealed that 1-3 complexed with KPC-2 adopted a "chair conformation" with the sulfate occupying the carboxylate binding region. The cefepime-2 and meropenem-3 combinations were effective in murine peritonitis and neutropenic lung infection models caused by MDR Acinetobacter baumannii. Compounds 1-3 are novel beta-lactamase inhibitors that demonstate potent cross-class inhibition, and clinical studies targeting MDR infections are warranted.

-	~~Authors~~: ~~van den Akker~~, F., Nguyen, N.Q.	+	Strategic Approaches to Overcome Resistance against Gram-Negative Pathogens Using beta-Lactamase Inhibitors and beta-Lactam Enhancers: Activity of Three Novel Diazabicyclooctanes WCK 5153, Zidebactam (WCK 5107), and WCK 4234.,Papp-Wallace KM, Nguyen NQ, Jacobs MR, Bethel CR, Barnes MD, Kumar V, Bajaksouzian S, Rudin SD, Rather PN, Bhavsar S, Ravikumar T, Deshpande PK, Patil V, Yeole R, Bhagwat SS, Patel MV, van den Akker F, Bonomo RA J Med Chem. 2018 May 10;61(9):4067-4086. doi: 10.1021/acs.jmedchem.8b00091. Epub , 2018 Apr 20. PMID:29627985<ref>PMID:29627985</ref>

-	~~Description: Crystal structure KPC~~-~~2 beta~~-~~lactamase complexed with WCK 5153 by co-crystallization~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Van Den~~ Akker, F]]	+	<div class="pdbe-citations 6b1y" style="background-color:#fffaf0;"></div>
-	[[Category: Nguyen, N.Q]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Beta-lactamase]]
		+	[[Category: Akker, F van den]]
		+	[[Category: Nguyen, N Q]]
		+	[[Category: Complex]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Inhibitor]]

OCA at 05:44, 25 October 2017

2017-10-25T05:44:20Z

←Older revision		Revision as of 05:44, 25 October 2017
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6b1y is ON HOLD	+	The entry 6b1y is ON HOLD until Paper Publication

	Authors: van den Akker, F., Nguyen, N.Q.		Authors: van den Akker, F., Nguyen, N.Q.
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	Description: Crystal structure KPC-2 beta-lactamase complexed with WCK 5153 by co-crystallization		Description: Crystal structure KPC-2 beta-lactamase complexed with WCK 5153 by co-crystallization
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Nguyen, N.Q]]
	[[Category: Van Den Akker, F]]		[[Category: Van Den Akker, F]]
		+	[[Category: Nguyen, N.Q]]

OCA: Protected "6b1y" [edit=sysop:move=sysop]

2017-09-27T17:04:37Z

Protected "6b1y" [edit=sysop:move=sysop]

←Older revision

Revision as of 17:04, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 6b1y is ON HOLD Authors: van den Akker, F., Nguyen, N.Q. Description: Crystal structure KPC-2 beta-lactamase complexed with WCK 5153 by co-crystall...

2017-09-27T17:04:36Z

New page: '''Unreleased structure''' The entry 6b1y is ON HOLD Authors: van den Akker, F., Nguyen, N.Q. Description: Crystal structure KPC-2 beta-lactamase complexed with WCK 5153 by co-crystall...

New page

'''Unreleased structure'''

The entry 6b1y is ON HOLD

Authors: van den Akker, F., Nguyen, N.Q.

Description: Crystal structure KPC-2 beta-lactamase complexed with WCK 5153 by co-crystallization
[[Category: Unreleased Structures]]
[[Category: Nguyen, N.Q]]
[[Category: Van Den Akker, F]]