7o0o - Revision history

OCA at 12:42, 1 February 2024

OCA — Thu, 01 Feb 2024 12:42:53 GMT

←Older revision		Revision as of 12:42, 1 February 2024
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	<StructureSection load='7o0o' size='340' side='right'caption='[[7o0o]], [[Resolution\|resolution]] 1.45Å' scene=''>		<StructureSection load='7o0o' size='340' side='right'caption='[[7o0o]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7o0o]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7O0O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O0O FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7o0o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Stenotrophomonas_maltophilia Stenotrophomonas maltophilia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7O0O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O0O FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9XS:(2~{S},3~{R},4~{S})-2-[(2~{S},3~{R})-1,3-bis(oxidanyl)-1-oxidanylidene-butan-2-yl]-4-[(3~{S},5~{S})-5-[(3-carboxyphenyl)carbamoyl]pyrrolidin-3-yl]sulfanyl-3-methyl-3,4-dihydro-2~{H}-pyrrole-5-carboxylic+acid'>9XS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.45Å</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9XS:(2~{S},3~{R},4~{S})-2-[(2~{S},3~{R})-1,3-bis(oxidanyl)-1-oxidanylidene-butan-2-yl]-4-[(3~{S},5~{S})-5-[(3-carboxyphenyl)carbamoyl]pyrrolidin-3-yl]sulfanyl-3-methyl-3,4-dihydro-2~{H}-pyrrole-5-carboxylic+acid'>9XS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7o0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o0o OCA], [https://pdbe.org/7o0o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o0o RCSB], [https://www.ebi.ac.uk/pdbsum/7o0o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o0o 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=7o0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o0o OCA], [https://pdbe.org/7o0o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o0o RCSB], [https://www.ebi.ac.uk/pdbsum/7o0o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o0o ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/BLA1_STEMA BLA1_STEMA]] Has a high activity against imipenem.	+	[https://www.uniprot.org/uniprot/BLA1_STEMA BLA1_STEMA] Has a high activity against imipenem.
	<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 7o0o" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7o0o" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta-lactamase 3D structures\|Beta-lactamase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Beta-lactamase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Hinchliffe, P~~]]	+	[[Category: Stenotrophomonas maltophilia]]
-	[[Category: ~~Spencer, J~~]]	+	[[Category: Hinchliffe P]]
-	[[Category: ~~Antibiotic]]~~	+	[[Category: Spencer J]]
-	~~[[Category: Antimicrobial protein]]~~	+
-	~~[[Category: Carbapenem]]~~	+
-	~~[[Category: Lactamase]]~~	+
-	~~[[Category: Ligand]]~~	+
-	~~[[Category: Metalloprotein~~]]	+

OCA at 11:03, 16 February 2022

OCA — Wed, 16 Feb 2022 11:03:58 GMT

←Older revision		Revision as of 11:03, 16 February 2022
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	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/BLA1_STEMA BLA1_STEMA]] Has a high activity against imipenem.		[[https://www.uniprot.org/uniprot/BLA1_STEMA BLA1_STEMA]] Has a high activity against imipenem.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Widespread bacterial resistance to carbapenem antibiotics is an increasing global health concern. Resistance has emerged due to carbapenem-hydrolyzing enzymes, including metallo-beta-lactamases (MbetaLs), but despite their prevalence and clinical importance, MbetaL mechanisms are still not fully understood. Carbapenem hydrolysis by MbetaLs can yield alternative product tautomers with the potential to access different binding modes. Here, we show that a combined approach employing crystallography and quantum mechanics/molecular mechanics (QM/MM) simulations allow tautomer assignment in MbetaL:hydrolyzed antibiotic complexes. Molecular simulations also examine (meta)stable species of alternative protonation and tautomeric states, providing mechanistic insights into beta-lactam hydrolysis. We report the crystal structure of the hydrolyzed carbapenem ertapenem bound to the L1 MbetaL from Stenotrophomonas maltophilia and model alternative tautomeric and protonation states of both hydrolyzed ertapenem and faropenem (a related penem antibiotic), which display different binding modes with L1. We show how the structures of both complexed beta-lactams are best described as the (2S)-imine tautomer with the carboxylate formed after beta-lactam ring cleavage deprotonated. Simulations show that enamine tautomer complexes are significantly less stable (e.g., showing partial loss of interactions with the L1 binuclear zinc center) and not consistent with experimental data. Strong interactions of Tyr32 and one zinc ion (Zn1) with ertapenem prevent a C6 group rotation, explaining the different binding modes of the two beta-lactams. Our findings establish the relative stability of different hydrolyzed (carba)penem forms in the L1 active site and identify interactions important to stable complex formation, information that should assist inhibitor design for this important antibiotic resistance determinant.
		+
		+	Crystallography and QM/MM Simulations Identify Preferential Binding of Hydrolyzed Carbapenem and Penem Antibiotics to the L1 Metallo-beta-Lactamase in the Imine Form.,Twidale RM, Hinchliffe P, Spencer J, Mulholland AJ J Chem Inf Model. 2021 Dec 27;61(12):5988-5999. doi: 10.1021/acs.jcim.1c00663., Epub 2021 Oct 12. PMID:34637298<ref>PMID:34637298</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7o0o" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 06:30, 1 December 2021

OCA — Wed, 01 Dec 2021 06:30:54 GMT

←Older revision		Revision as of 06:30, 1 December 2021
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	==Crystal structure of the B3 metallo-beta-lactamase L1 with hydrolysed ertapenem==		==Crystal structure of the B3 metallo-beta-lactamase L1 with hydrolysed ertapenem==
-	<StructureSection load='7o0o' size='340' side='right'caption='[[7o0o]]' scene=''>	+	<StructureSection load='7o0o' size='340' side='right'caption='[[7o0o]], [[Resolution\|resolution]] 1.45Å' 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=7O0O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O0O FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7o0o]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7O0O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O0O 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=7o0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o0o OCA], [https://pdbe.org/7o0o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o0o RCSB], [https://www.ebi.ac.uk/pdbsum/7o0o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o0o 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=9XS:(2~{S},3~{R},4~{S})-2-[(2~{S},3~{R})-1,3-bis(oxidanyl)-1-oxidanylidene-butan-2-yl]-4-[(3~{S},5~{S})-5-[(3-carboxyphenyl)carbamoyl]pyrrolidin-3-yl]sulfanyl-3-methyl-3,4-dihydro-2~{H}-pyrrole-5-carboxylic+acid'>9XS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=7o0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o0o OCA], [https://pdbe.org/7o0o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o0o RCSB], [https://www.ebi.ac.uk/pdbsum/7o0o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o0o ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/BLA1_STEMA BLA1_STEMA]] Has a high activity against imipenem.
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Beta-lactamase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Hinchliffe P]]	+	[[Category: Hinchliffe, P]]
-	[[Category: Spencer J]]	+	[[Category: Spencer, J]]
		+	[[Category: Antibiotic]]
		+	[[Category: Antimicrobial protein]]
		+	[[Category: Carbapenem]]
		+	[[Category: Lactamase]]
		+	[[Category: Ligand]]
		+	[[Category: Metalloprotein]]

OCA at 11:43, 13 October 2021

OCA — Wed, 13 Oct 2021 11:43:42 GMT

←Older revision		Revision as of 11:43, 13 October 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7o0o ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of the B3 metallo-beta-lactamase L1 with hydrolysed ertapenem==
-		+	<StructureSection load='7o0o' size='340' side='right'caption='[[7o0o]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7O0O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O0O 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=7o0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o0o OCA], [https://pdbe.org/7o0o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o0o RCSB], [https://www.ebi.ac.uk/pdbsum/7o0o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o0o ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Hinchliffe P]]
		+	[[Category: Spencer J]]

OCA at 07:32, 5 May 2021

OCA — Wed, 05 May 2021 07:32:43 GMT

←Older revision		Revision as of 07:32, 5 May 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7o0o is ON HOLD	+	The entry 7o0o is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7o0o" [edit=sysop:move=sysop]

OCA — Wed, 07 Apr 2021 04:49:00 GMT

Protected "7o0o" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:49, 7 April 2021

OCA: New page: '''Unreleased structure''' The entry 7o0o is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 07 Apr 2021 04:48:58 GMT

New page: '''Unreleased structure''' The entry 7o0o is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7o0o is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]