7a60 - Revision history

OCA at 12:04, 1 February 2024

OCA — Thu, 01 Feb 2024 12:04:13 GMT

←Older revision		Revision as of 12:04, 1 February 2024
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	<StructureSection load='7a60' size='340' side='right'caption='[[7a60]], [[Resolution\|resolution]] 1.47Å' scene=''>		<StructureSection load='7a60' size='340' side='right'caption='[[7a60]], [[Resolution\|resolution]] 1.47Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7a60]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A60 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A60 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7a60]] is a 2 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=7A60 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A60 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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]] 1.47Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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=7a60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a60 OCA], [https://pdbe.org/7a60 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a60 RCSB], [https://www.ebi.ac.uk/pdbsum/7a60 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a60 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=7a60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a60 OCA], [https://pdbe.org/7a60 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a60 RCSB], [https://www.ebi.ac.uk/pdbsum/7a60 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a60 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 ==
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	</div>		</div>
	<div class="pdbe-citations 7a60" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7a60" 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: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Hinchliffe, P~~]]	+	[[Category: Pseudomonas aeruginosa]]
-	[[Category: ~~Spencer, J~~]]	+	[[Category: Hinchliffe P]]
-	[[Category: ~~Antibiotic]]~~	+	[[Category: Spencer J]]
-	~~[[Category: Antimicrobial protein]]~~	+
-	~~[[Category: Catalysis]]~~	+
-	~~[[Category: Faropenem]]~~	+
-	~~[[Category: Metallo-beta-lactamase~~]]	+

OCA at 15:00, 3 March 2021

OCA — Wed, 03 Mar 2021 15:00:40 GMT

←Older revision		Revision as of 15:00, 3 March 2021
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	==Crystal structure of VIM-2 with hydrolyzed faropenem (ring-open form)==		==Crystal structure of VIM-2 with hydrolyzed faropenem (ring-open form)==
-	<StructureSection load='7a60' size='340' side='right'caption='[[7a60]]' scene=''>	+	<StructureSection load='7a60' size='340' side='right'caption='[[7a60]], [[Resolution\|resolution]] 1.47Å' 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=7A60 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A60 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7a60]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A60 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A60 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=7a60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a60 OCA], [https://pdbe.org/7a60 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a60 RCSB], [https://www.ebi.ac.uk/pdbsum/7a60 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a60 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=FMT:FORMIC+ACID'>FMT</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=7a60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a60 OCA], [https://pdbe.org/7a60 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a60 RCSB], [https://www.ebi.ac.uk/pdbsum/7a60 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a60 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 7a60" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Hinchliffe P]]	+	[[Category: Hinchliffe, P]]
-	[[Category: Spencer J]]	+	[[Category: Spencer, J]]
		+	[[Category: Antibiotic]]
		+	[[Category: Antimicrobial protein]]
		+	[[Category: Catalysis]]
		+	[[Category: Faropenem]]
		+	[[Category: Metallo-beta-lactamase]]

OCA at 06:39, 24 February 2021

OCA — Wed, 24 Feb 2021 06:39:29 GMT

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

-	~~The entry 7a60 is ON HOLD until Paper Publication~~	+	==Crystal structure of VIM-2 with hydrolyzed faropenem (ring-open form)==
-		+	<StructureSection load='7a60' size='340' side='right'caption='[[7a60]]' scene=''>
-	~~Authors: Hinchliffe, P., Spencer, J.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A60 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A60 FirstGlance]. <br>
-	~~Description:~~ Crystal structure of VIM-2 with hydrolyzed faropenem (ring-open form)	+	</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=7a60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a60 OCA], [https://pdbe.org/7a60 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a60 RCSB], [https://www.ebi.ac.uk/pdbsum/7a60 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a60 ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Spencer~~, J]]	+	__TOC__
-	[[Category: Hinchliffe, P]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Hinchliffe P]]
		+	[[Category: Spencer J]]

OCA at 08:38, 23 September 2020

OCA — Wed, 23 Sep 2020 08:38:12 GMT

←Older revision		Revision as of 08:38, 23 September 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7a60 is ON HOLD	+	The entry 7a60 is ON HOLD until Paper Publication

	Authors: Hinchliffe, P., Spencer, J.		Authors: Hinchliffe, P., Spencer, J.

OCA: Protected "7a60" [edit=sysop:move=sysop]

OCA — Wed, 02 Sep 2020 05:04:35 GMT

Protected "7a60" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:04, 2 September 2020

OCA: New page: '''Unreleased structure''' The entry 7a60 is ON HOLD Authors: Hinchliffe, P., Spencer, J. Description: Crystal structure of VIM-2 with hydrolyzed faropenem (ring-open form) [[Category:...

OCA — Wed, 02 Sep 2020 05:04:33 GMT

New page: '''Unreleased structure''' The entry 7a60 is ON HOLD Authors: Hinchliffe, P., Spencer, J. Description: Crystal structure of VIM-2 with hydrolyzed faropenem (ring-open form) [[Category:...

New page

'''Unreleased structure'''

The entry 7a60 is ON HOLD

Authors: Hinchliffe, P., Spencer, J.

Description: Crystal structure of VIM-2 with hydrolyzed faropenem (ring-open form)
[[Category: Unreleased Structures]]
[[Category: Spencer, J]]
[[Category: Hinchliffe, P]]