5xhr - Revision history

OCA at 08:02, 22 November 2023

2023-11-22T08:02:26Z

←Older revision		Revision as of 08:02, 22 November 2023
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	==Crystal structure of P99 beta-lactamase in complex with a penicillin derivative MPC-1==		==Crystal structure of P99 beta-lactamase in complex with a penicillin derivative MPC-1==
-	<StructureSection load='5xhr' size='340' side='right' caption='[[5xhr]], [[Resolution\|resolution]] 1.80Å' scene=''>	+	<StructureSection load='5xhr' size='340' side='right'caption='[[5xhr]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5xhr]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"aerobacter_cloacae"_(jordan_1890)_bergey_et_al._1923 "aerobacter~~ cloacae~~" (jordan 1890) bergey et al. 1923~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XHR OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5XHR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5xhr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterobacter_cloacae Enterobacter cloacae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XHR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XHR FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PXH:(2~{R},4~{S})-5,5-dimethyl-2-[(2~{S},3~{R})-3-oxidanyl-1-oxidanylidene-5-thiophen-2-yl-pentan-2-yl]-1,3-thiazolidine-4-carboxylic+acid'>PXH</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]] 1.8Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ampC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=550 "Aerobacter cloacae" (Jordan 1890) Bergey et al. 1923])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PXH:(2~{R},4~{S})-5,5-dimethyl-2-[(2~{S},3~{R})-3-oxidanyl-1-oxidanylidene-5-thiophen-2-yl-pentan-2-yl]-1,3-thiazolidine-4-carboxylic+acid'>PXH</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=5xhr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xhr OCA], [https://pdbe.org/5xhr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xhr RCSB], [https://www.ebi.ac.uk/pdbsum/5xhr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xhr ProSAT]</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=5xhr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xhr OCA], [~~http~~://pdbe.org/5xhr PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5xhr RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5xhr PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5xhr ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/AMPC_ENTCL AMPC_ENTCL]] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.	+	[https://www.uniprot.org/uniprot/AMPC_ENTCL AMPC_ENTCL] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5xhr" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5xhr" 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: Enterobacter cloacae]]
-	[[Category: ~~Pan, X~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Zhao, Y~~]]	+	[[Category: Pan X]]
-	[[Category: ~~Hydrolase~~]]	+	[[Category: Zhao Y]]

OCA at 07:55, 6 December 2017

2017-12-06T07:55:39Z

←Older revision		Revision as of 07:55, 6 December 2017
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	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/AMPC_ENTCL AMPC_ENTCL]] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.		[[http://www.uniprot.org/uniprot/AMPC_ENTCL AMPC_ENTCL]] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Bacterial beta-lactamases readily inactivate most penicillins and cephalosporins by hydrolyzing and "opening" their signature beta-lactam ring. In contrast, carbapenems resist hydrolysis by many serine-based class A, C, and D beta-lactamases due to their unique stereochemical features. To improve the resistance profile of penicillins, we synthesized a modified penicillin molecule, MPC-1, by "grafting" carbapenem-like stereochemistry onto the penicillin core. Chemical modifications include the trans conformation of hydrogen atoms at C-5 and C-6 instead of cis, and a 6-alpha hydroxyethyl moiety to replace the original 6-beta aminoacyl group. MPC-1 selectively inhibits class C beta-lactamases, such as P99, by forming a nonhydrolyzable acyl adduct, and its inhibitory potency is approximately 2 to 5 times higher than that for clinically used beta-lactamase inhibitors clavulanate and sulbactam. The crystal structure of MPC-1 forming the acyl adduct with P99 reveals a novel binding mode for MPC-1 that resembles carbapenem bound in the active site of class A beta-lactamases. Furthermore, in this novel binding mode, the carboxyl group of MPC-1 blocks the deacylation reaction by occluding the critical catalytic water molecule and renders the acyl adduct nonhydrolyzable. Our results suggest that by incorporating carbapenem-like stereochemistry, the current collection of over 100 penicillins and cephalosporins can be modified into candidate compounds for development of novel beta-lactamase inhibitors.
		+
		+	Modified Penicillin Molecule with Carbapenem-Like Stereochemistry Specifically Inhibits Class C beta-Lactamases.,Pan X, He Y, Chen T, Chan KF, Zhao Y Antimicrob Agents Chemother. 2017 Nov 22;61(12). pii: AAC.01288-17. doi:, 10.1128/AAC.01288-17. Print 2017 Dec. PMID:28971874<ref>PMID:28971874</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5xhr" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 11:49, 6 November 2017

2017-11-06T11:49:29Z

←Older revision		Revision as of 11:49, 6 November 2017
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-	'''Unreleased structure'''

-	~~The entry~~ 5xhr is ~~ON HOLD~~	+	==Crystal structure of P99 beta-lactamase in complex with a penicillin derivative MPC-1==
-		+	<StructureSection load='5xhr' size='340' side='right' caption='[[5xhr]], [[Resolution\|resolution]] 1.80Å' scene=''>
-	~~Authors~~: ~~Pan~~, X., ~~Zhao~~, Y.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5xhr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"aerobacter_cloacae"_(jordan_1890)_bergey_et_al._1923 "aerobacter cloacae" (jordan 1890) bergey et al. 1923]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XHR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XHR FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure of P99~~ beta-lactamase ~~in complex~~ with a ~~penicillin derivative PC1~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PXH:(2~{R},4~{S})-5,5-dimethyl-2-[(2~{S},3~{R})-3-oxidanyl-1-oxidanylidene-5-thiophen-2-yl-pentan-2-yl]-1,3-thiazolidine-4-carboxylic+acid'>PXH</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ampC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=550 "Aerobacter cloacae" (Jordan 1890) Bergey et al. 1923])</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=5xhr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xhr OCA], [http://pdbe.org/5xhr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xhr RCSB], [http://www.ebi.ac.uk/pdbsum/5xhr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xhr ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/AMPC_ENTCL AMPC_ENTCL]] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Beta-lactamase]]
		+	[[Category: Pan, X]]
	[[Category: Zhao, Y]]		[[Category: Zhao, Y]]
-	[[Category: ~~Pan, X~~]]	+	[[Category: Hydrolase]]

OCA: Protected "5xhr" [edit=sysop:move=sysop]

2017-05-04T12:12:56Z

Protected "5xhr" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:12, 4 May 2017

OCA: New page: '''Unreleased structure''' The entry 5xhr is ON HOLD Authors: Pan, X., Zhao, Y. Description: Crystal structure of P99 beta-lactamase in complex with a penicillin derivative PC1 [[Categ...

2017-05-04T12:12:54Z

New page: '''Unreleased structure''' The entry 5xhr is ON HOLD Authors: Pan, X., Zhao, Y. Description: Crystal structure of P99 beta-lactamase in complex with a penicillin derivative PC1 [[Categ...

New page

'''Unreleased structure'''

The entry 5xhr is ON HOLD

Authors: Pan, X., Zhao, Y.

Description: Crystal structure of P99 beta-lactamase in complex with a penicillin derivative PC1
[[Category: Unreleased Structures]]
[[Category: Zhao, Y]]
[[Category: Pan, X]]