7kiv - Revision history

OCA at 15:25, 18 October 2023

2023-10-18T15:25:54Z

←Older revision		Revision as of 15:25, 18 October 2023
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	<StructureSection load='7kiv' size='340' side='right'caption='[[7kiv]], [[Resolution\|resolution]] 2.39Å' scene=''>		<StructureSection load='7kiv' size='340' side='right'caption='[[7kiv]], [[Resolution\|resolution]] 2.39Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7kiv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Pseae Pseae~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KIV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KIV FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7kiv]] is a 1 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=7KIV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KIV FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=NXL:(2S~~,~~5R)-1-FORMYL-5-~~[~~(SULFOOXY)AMINO~~]~~PIPERIDINE-~~2~~-CARBOXAMIDE'>NXL</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]] 2.389Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>ftsI, pbpB, PA4418 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id~~=208964 PSEAE])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NXL:(2S,5R)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>NXL</scene></td></tr>
-	~~<tr id='activity'><td class~~="~~sblockLbl~~"><~~b>Activity:</b></td><td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[https~~:~~//en.wikipedia.org/wiki/Serine~~-~~type_D~~-~~Ala~~-D-~~Ala_carboxypeptidase Serine~~-~~type D~~-~~Ala-D-Ala carboxypeptidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.16.4 3.4.16.4]~~ </~~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=7kiv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kiv OCA], [https://pdbe.org/7kiv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kiv RCSB], [https://www.ebi.ac.uk/pdbsum/7kiv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kiv 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=7kiv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kiv OCA], [https://pdbe.org/7kiv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kiv RCSB], [https://www.ebi.ac.uk/pdbsum/7kiv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kiv ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/FTSI_PSEAE FTSI_PSEAE]] Catalyzes cross-linking of the peptidoglycan cell wall at the division septum (By similarity). Binds penicillin (PubMed:20580675).[HAMAP-Rule:MF_02080]<ref>PMID:20580675</ref>	+	[https://www.uniprot.org/uniprot/FTSI_PSEAE FTSI_PSEAE] Catalyzes cross-linking of the peptidoglycan cell wall at the division septum (By similarity). Binds penicillin (PubMed:20580675).[HAMAP-Rule:MF_02080]<ref>PMID:20580675</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 7kiv" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7kiv" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Penicillin-binding protein 3D structures\|Penicillin-binding protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Pseae]]~~	+	[[Category: Pseudomonas aeruginosa PAO1]]
-	~~[[Category: Serine-type D-Ala-D-Ala carboxypeptidase~~]]	+	[[Category: Van den Akker F]]
-	[[Category: Akker, F ~~van den]]~~	+
-	~~[[Category: Antibiotic resistance]]~~	+
-	~~[[Category: Cell wall]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Hydrolase-inhibitor-antibiotic complex]]~~	+
-	~~[[Category: Inhibitor~~]]	+

OCA at 15:03, 3 March 2021

2021-03-03T15:03:42Z

←Older revision		Revision as of 15:03, 3 March 2021
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	==Crystal structure of Pseudomonas aeruginosa PBP3 in complex with avibactam==		==Crystal structure of Pseudomonas aeruginosa PBP3 in complex with avibactam==
-	<StructureSection load='7kiv' size='340' side='right'caption='[[7kiv]]' scene=''>	+	<StructureSection load='7kiv' size='340' side='right'caption='[[7kiv]], [[Resolution\|resolution]] 2.39Å' 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=7KIV OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=7KIV FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7kiv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseae Pseae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KIV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KIV FirstGlance]. <br>
-	</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=7kiv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kiv OCA], [~~http~~://pdbe.org/7kiv PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7kiv RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7kiv PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7kiv 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=NXL:(2S,5R)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>NXL</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ftsI, pbpB, PA4418 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=208964 PSEAE])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Serine-type_D-Ala-D-Ala_carboxypeptidase Serine-type D-Ala-D-Ala carboxypeptidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.16.4 3.4.16.4] </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=7kiv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kiv OCA], [https://pdbe.org/7kiv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kiv RCSB], [https://www.ebi.ac.uk/pdbsum/7kiv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kiv ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/FTSI_PSEAE FTSI_PSEAE]] Catalyzes cross-linking of the peptidoglycan cell wall at the division septum (By similarity). Binds penicillin (PubMed:20580675).[HAMAP-Rule:MF_02080]<ref>PMID:20580675</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Multidrug-resistant (MDR) pathogens pose a significant public health threat. A major mechanism of resistance expressed by MDR pathogens is beta-lactamase-mediated degradation of beta-lactam antibiotics. The diazabicyclooctane (DBO) compounds zidebactam and WCK 5153, recognized as beta-lactam "enhancers" due to inhibition of Pseudomonas aeruginosa penicillin-binding protein 2 (PBP2), are also class A and C beta-lactamase inhibitors. To structurally probe their mode of PBP2 inhibition as well as investigate why P. aeruginosa PBP2 is less susceptible to inhibition by beta-lactam antibiotics compared to the Escherichia coli PBP2, we determined the crystal structure of P. aeruginosa PBP2 in complex with WCK 5153. WCK 5153 forms an inhibitory covalent bond with the catalytic S327 of PBP2. The structure suggests a significant role for the diacylhydrazide moiety of WCK 5153 in interacting with the aspartate in the S-X-N/D PBP motif. Modeling of zidebactam in the active site of PBP2 reveals a similar binding mode. Both DBOs increase the melting temperature of PBP2, affirming their stabilizing interactions. To aid in the design of DBOs that can inhibit multiple PBPs, the ability of three DBOs to interact with P. aeruginosa PBP3 was explored crystallographically. Even though the DBOs show covalent binding to PBP3, they destabilized PBP3. Overall, the studies provide insights into zidebactam and WCK 5153 inhibition of PBP2 compared to their inhibition of PBP3 and the evolutionarily related KPC-2 beta-lactamase. These molecular insights into the dual-target DBOs advance our knowledge regarding further DBO optimization efforts to develop novel potent beta-lactamase-resistant, non-beta-lactam PBP inhibitors.IMPORTANCE Antibiotic resistance is a significant clinical problem. Developing novel antibiotics that overcome known resistance mechanisms is highly desired. Diazabicyclooctane inhibitors such as zidebactam possess this potential as they readily inactivate penicillin-binding proteins, yet cannot be degraded by beta-lactamases. In this study, we characterized the inhibition by diazabicyclooctanes of penicillin-binding proteins PBP2 and PBP3 from Pseudomonas aeruginosa using protein crystallography and biophysical analyses. These structures and analyses help define the antibiotic properties of these inhibitors, explain the decreased susceptibility of P. aeruginosa PBP2 to be inhibited by beta-lactam antibiotics, and provide insights that could be used for further antibiotic development.
		+
		+	Structural Characterization of Diazabicyclooctane beta-Lactam "Enhancers" in Complex with Penicillin-Binding Proteins PBP2 and PBP3 of Pseudomonas aeruginosa.,Rajavel M, Kumar V, Nguyen H, Wyatt J, Marshall SH, Papp-Wallace KM, Deshpande P, Bhavsar S, Yeole R, Bhagwat S, Patel M, Bonomo RA, van den Akker F mBio. 2021 Feb 16;12(1). pii: mBio.03058-20. doi: 10.1128/mBio.03058-20. PMID:33593978<ref>PMID:33593978</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7kiv" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Van den~~ Akker F]]	+	[[Category: Pseae]]
		+	[[Category: Serine-type D-Ala-D-Ala carboxypeptidase]]
		+	[[Category: Akker, F van den]]
		+	[[Category: Antibiotic resistance]]
		+	[[Category: Cell wall]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-inhibitor-antibiotic complex]]
		+	[[Category: Inhibitor]]

OCA at 05:56, 20 January 2021

2021-01-20T05:56:32Z

←Older revision		Revision as of 05:56, 20 January 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7kiv ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of Pseudomonas aeruginosa PBP3 in complex with avibactam==
-		+	<StructureSection load='7kiv' size='340' side='right'caption='[[7kiv]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KIV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7KIV FirstGlance]. <br>
-	~~Description~~:	+	</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=7kiv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kiv OCA], [http://pdbe.org/7kiv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7kiv RCSB], [http://www.ebi.ac.uk/pdbsum/7kiv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7kiv ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Van den Akker F]]

OCA at 05:46, 2 December 2020

2020-12-02T05:46:45Z

←Older revision		Revision as of 05:46, 2 December 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7kiv is ON HOLD	+	The entry 7kiv is ON HOLD until Paper Publication

	Authors:		Authors:

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

2020-11-04T05:37:20Z

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

←Older revision

Revision as of 05:37, 4 November 2020

OCA: New page: '''Unreleased structure''' The entry 7kiv is ON HOLD Authors: Description: Category: Unreleased Structures

2020-11-04T05:37:19Z

New page: '''Unreleased structure''' The entry 7kiv is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7kiv is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]