7a5z - Revision history

OCA at 12:04, 1 February 2024

OCA — Thu, 01 Feb 2024 12:04:12 GMT

←Older revision		Revision as of 12:04, 1 February 2024
Line 3:		Line 3:
	<StructureSection load='7a5z' size='340' side='right'caption='[[7a5z]], [[Resolution\|resolution]] 1.29Å' scene=''>		<StructureSection load='7a5z' size='340' side='right'caption='[[7a5z]], [[Resolution\|resolution]] 1.29Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7a5z]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A5Z FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7a5z]] is a 1 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=7A5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A5Z 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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=QZH:(5~{Z})-2-[1,3-bis(oxidanyl)-1-oxidanylidene-butan-2-yl]-5-(4-oxidanylbutylidene)-2~{H}-1,3-thiazole-4-carboxylic+acid'>QZH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.29Å</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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=QZH:(5~{Z})-2-[1,3-bis(oxidanyl)-1-oxidanylidene-butan-2-yl]-5-(4-oxidanylbutylidene)-2~{H}-1,3-thiazole-4-carboxylic+acid'>QZH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7a5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a5z OCA], [https://pdbe.org/7a5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a5z RCSB], [https://www.ebi.ac.uk/pdbsum/7a5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a5z 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=7a5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a5z OCA], [https://pdbe.org/7a5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a5z RCSB], [https://www.ebi.ac.uk/pdbsum/7a5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a5z ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q9K2N0_PSEAI Q9K2N0_PSEAI]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 24:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Lucic, A~~]]	+	[[Category: Pseudomonas aeruginosa]]
-	[[Category: ~~Schofield, C J~~]]	+	[[Category: Lucic A]]
-	[[Category: ~~Antimicrobial protein]]~~	+	[[Category: Schofield CJ]]
-	~~[[Category: Antimicrobial resistance]]~~	+
-	~~[[Category: Carbapenem]]~~	+
-	~~[[Category: Faropenem]]~~	+
-	~~[[Category: Metallo-beta-lactamase]]~~	+
-	~~[[Category: Penem]]~~	+
-	~~[[Category: Vim-2~~]]	+

OCA at 15:00, 3 March 2021

OCA — Wed, 03 Mar 2021 15:00:25 GMT

←Older revision		Revision as of 15:00, 3 March 2021
Line 1:		Line 1:

	==Structure of VIM-2 metallo-beta-lactamase with hydrolysed Faropenem imine product==		==Structure of VIM-2 metallo-beta-lactamase with hydrolysed Faropenem imine product==
-	<StructureSection load='7a5z' size='340' side='right'caption='[[7a5z]]' scene=''>	+	<StructureSection load='7a5z' size='340' side='right'caption='[[7a5z]], [[Resolution\|resolution]] 1.29Å' 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=7A5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A5Z FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7a5z]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A5Z 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=7a5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a5z OCA], [https://pdbe.org/7a5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a5z RCSB], [https://www.ebi.ac.uk/pdbsum/7a5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a5z 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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=QZH:(5~{Z})-2-[1,3-bis(oxidanyl)-1-oxidanylidene-butan-2-yl]-5-(4-oxidanylbutylidene)-2~{H}-1,3-thiazole-4-carboxylic+acid'>QZH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7a5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a5z OCA], [https://pdbe.org/7a5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a5z RCSB], [https://www.ebi.ac.uk/pdbsum/7a5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a5z ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Penems have demonstrated potential as antibacterials and beta-lactamase inhibitors; however, their clinical use has been limited, especially in comparison with the structurally related carbapenems. Faropenem is an orally active antibiotic with a C-2 tetrahydrofuran (THF) ring, which is resistant to hydrolysis by some beta-lactamases. We report studies on the reactions of faropenem with carbapenem-hydrolysing beta-lactamases, focusing on the class A serine beta-lactamase KPC-2 and the metallo beta-lactamases (MBLs) VIM-2 (a subclass B1 MBL) and L1 (a B3 MBL). Kinetic studies show that faropenem is a substrate for all three beta-lactamases, though it is less efficiently hydrolysed by KPC-2. Crystallographic analyses on faropenem-derived complexes reveal opening of the beta-lactam ring with formation of an imine with KPC-2, VIM-2, and L1. In the cases of the KPC-2 and VIM-2 structures, the THF ring is opened to give an alkene, but with L1 the THF ring remains intact. Solution state studies, employing NMR, were performed on L1, KPC-2, VIM-2, VIM-1, NDM-1, OXA-23, OXA-10, and OXA-48. The solution results reveal, in all cases, formation of imine products in which the THF ring is opened; formation of a THF ring-closed imine product was only observed with VIM-1 and VIM-2. An enamine product with a closed THF ring was also observed in all cases, at varying levels. Combined with previous reports, the results exemplify the potential for different outcomes in the reactions of penems with MBLs and SBLs and imply further structure-activity relationship studies are worthwhile to optimise the interactions of penems with beta-lactamases. They also exemplify how crystal structures of beta-lactamase substrate/inhibitor complexes do not always reflect reaction outcomes in solution.
		+
		+	Faropenem reacts with serine and metallo-beta-lactamases to give multiple products.,Lucic A, Hinchliffe P, Malla TR, Tooke CL, Brem J, Calvopina K, Lohans CT, Rabe P, McDonough MA, Armistead T, Orville AM, Spencer J, Schofield CJ Eur J Med Chem. 2021 Feb 9;215:113257. doi: 10.1016/j.ejmech.2021.113257. PMID:33618159<ref>PMID:33618159</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7a5z" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Lucic A]]	+	[[Category: Lucic, A]]
-	[[Category: Schofield CJ]]	+	[[Category: Schofield, C J]]
		+	[[Category: Antimicrobial protein]]
		+	[[Category: Antimicrobial resistance]]
		+	[[Category: Carbapenem]]
		+	[[Category: Faropenem]]
		+	[[Category: Metallo-beta-lactamase]]
		+	[[Category: Penem]]
		+	[[Category: Vim-2]]

OCA at 06:39, 24 February 2021

OCA — Wed, 24 Feb 2021 06:39:27 GMT

←Older revision		Revision as of 06:39, 24 February 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7a5z is ON HOLD until Paper Publication~~	+	==Structure of VIM-2 metallo-beta-lactamase with hydrolysed Faropenem imine product==
-		+	<StructureSection load='7a5z' size='340' side='right'caption='[[7a5z]]' scene=''>
-	~~Authors: Lucic, A., Schofield, C.J.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A5Z FirstGlance]. <br>
-	~~Description:~~ Structure of VIM-2 metallo-beta-lactamase with hydrolysed Faropenem imine product	+	</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=7a5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a5z OCA], [https://pdbe.org/7a5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a5z RCSB], [https://www.ebi.ac.uk/pdbsum/7a5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a5z ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Lucic, A]]	+	__TOC__
-	[[Category: Schofield~~, C.J~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Lucic A]]
		+	[[Category: Schofield CJ]]

OCA at 05:16, 4 November 2020

OCA — Wed, 04 Nov 2020 05:16:40 GMT

←Older revision		Revision as of 05:16, 4 November 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7a5z is ON HOLD	+	The entry 7a5z is ON HOLD until Paper Publication

	Authors: Lucic, A., Schofield, C.J.		Authors: Lucic, A., Schofield, C.J.

OCA: Protected "7a5z" [edit=sysop:move=sysop]

OCA — Wed, 02 Sep 2020 05:04:30 GMT

Protected "7a5z" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:04, 2 September 2020

OCA: New page: '''Unreleased structure''' The entry 7a5z is ON HOLD Authors: Lucic, A., Schofield, C.J. Description: Structure of VIM-2 metallo-beta-lactamase with hydrolysed Faropenem imine product ...

OCA — Wed, 02 Sep 2020 05:04:29 GMT

New page: '''Unreleased structure''' The entry 7a5z is ON HOLD Authors: Lucic, A., Schofield, C.J. Description: Structure of VIM-2 metallo-beta-lactamase with hydrolysed Faropenem imine product ...

New page

'''Unreleased structure'''

The entry 7a5z is ON HOLD

Authors: Lucic, A., Schofield, C.J.

Description: Structure of VIM-2 metallo-beta-lactamase with hydrolysed Faropenem imine product
[[Category: Unreleased Structures]]
[[Category: Lucic, A]]
[[Category: Schofield, C.J]]