4n92 - Revision history

OCA at 08:56, 20 March 2024

OCA — Wed, 20 Mar 2024 08:56:47 GMT

←Older revision		Revision as of 08:56, 20 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4n92]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_licheniformis Bacillus licheniformis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N92 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N92 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4n92]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_licheniformis Bacillus licheniformis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N92 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N92 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=4n92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n92 OCA], [https://pdbe.org/4n92 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n92 RCSB], [https://www.ebi.ac.uk/pdbsum/4n92 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n92 ProSAT]</span></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]] 1.93Å</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=4n92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n92 OCA], [https://pdbe.org/4n92 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n92 RCSB], [https://www.ebi.ac.uk/pdbsum/4n92 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n92 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/BLAC_BACLI BLAC_BACLI]		[https://www.uniprot.org/uniprot/BLAC_BACLI BLAC_BACLI]
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Most class A beta-lactamases cannot hydrolyze carbapenem antibiotics effectively. The molecular mechanism of this catalytic inefficiency has been attributed to the unique stereochemistry of carbapenems, including their 6-alpha-hydroxyethyl side chain and the transition between two tautomeric states when bound at the active site. Previous studies have shown that the 6-alpha-hydroxyethyl side chain of carbapenems can interfere with catalysis by forming hydrogen bonds with the deacylation water molecule to reduce its nucleophilicity. Here our studies of a class A noncarbapenemase PenP demonstrate that substituting the general base residue Glu166 with Ser or other residues leads to a significant enhancement of the acylation kinetics by approximately 100-500 times toward carbapenems like meropenem. The structures of PenP and Glu166Ser both in apo form and in complex with meropenem reveal that Glu166 is critical for the formation of a hydrogen bonding network within the active site that locks Asn170 in an orientation to impose steric clash with the 6-alpha-hydroxyethyl side chain of meropenem. The Glu166Ser substitution weakens this network and enables Asn170 to adopt an alternative conformation to avoid steric clash and accommodate faster acylation kinetics. Furthermore, the weakened hydrogen bonding network caused by the Glu166Ser substitution allows the 6-alpha-hydroxyethyl moiety to adopt a catalytically favorable orientation as seen in class A carbapenemases. In summary, our data identify a previously unreported role of the universally conserved general base residue Glu166 in impeding the proper binding of carbapenems by restricting their 6-alpha-hydroxyethyl group.
-
-	Perturbing the General Base Residue Glu166 in the Active Site of Class A beta-Lactamase Leads to Enhanced Carbapenem Binding and Acylation.,Pan X, Wong WT, He Y, Jiang Y, Zhao Y Biochemistry. 2014 Aug 26;53(33):5414-23. doi: 10.1021/bi401609h. Epub 2014 Aug, 15. PMID:25020031<ref>PMID:25020031</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4n92" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Beta-lactamase 3D structures\|Beta-lactamase 3D structures]]		*[[Beta-lactamase 3D structures\|Beta-lactamase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 08:15, 11 January 2023

OCA — Wed, 11 Jan 2023 08:15:22 GMT

←Older revision		Revision as of 08:15, 11 January 2023
Line 3:		Line 3:
	<StructureSection load='4n92' size='340' side='right'caption='[[4n92]], [[Resolution\|resolution]] 1.93Å' scene=''>		<StructureSection load='4n92' size='340' side='right'caption='[[4n92]], [[Resolution\|resolution]] 1.93Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4n92]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"clostridium_licheniforme"_weigmann_1898 "clostridium licheniforme" weigmann 1898~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N92 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4N92 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4n92]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_licheniformis Bacillus licheniformis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N92 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N92 FirstGlance]. <br>
-	</td></tr>~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4n9k\|4n9k]], [[4n9l\|4n9l]]</td></tr>~~	+	</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=4n92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n92 OCA], [https://pdbe.org/4n92 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n92 RCSB], [https://www.ebi.ac.uk/pdbsum/4n92 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n92 ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">blaP, penP, penP blaP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1402 "Clostridium licheniforme" Weigmann 1898])</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=4n92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n92 OCA], [~~http~~://pdbe.org/4n92 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4n92 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4n92 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4n92 ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/BLAC_BACLI BLAC_BACLI]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 19:

	==See Also==		==See Also==
-	*[[Beta-lactamase\|Beta-lactamase]]	+	*[[Beta-lactamase 3D structures\|Beta-lactamase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Clostridium licheniforme weigmann 1898]]~~	+	[[Category: Bacillus licheniformis]]
-	~~[[Category: Beta-lactamase~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Pan, X]]	+	[[Category: Pan X]]
-	[[Category: Wong, W]]	+	[[Category: Wong W]]
-	[[Category: Zhao, Y]]	+	[[Category: Zhao Y]]
-	~~[[Category: Hydrolase~~]]	+

OCA at 08:14, 10 April 2019

OCA — Wed, 10 Apr 2019 08:14:42 GMT

←Older revision		Revision as of 08:14, 10 April 2019
Line 1:		Line 1:

	==Crystal structure of beta-lactamse PenP_E166S==		==Crystal structure of beta-lactamse PenP_E166S==
-	<StructureSection load='4n92' size='340' side='right' caption='[[4n92]], [[Resolution\|resolution]] 1.93Å' scene=''>	+	<StructureSection load='4n92' size='340' side='right'caption='[[4n92]], [[Resolution\|resolution]] 1.93Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4n92]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N92 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4N92 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4n92]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"clostridium_licheniforme"_weigmann_1898 "clostridium licheniforme" weigmann 1898]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N92 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4N92 FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4n9k\|4n9k]], [[4n9l\|4n9l]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4n9k\|4n9k]], [[4n9l\|4n9l]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">blaP, penP, penP blaP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1402 "Clostridium licheniforme" Weigmann 1898])</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='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=4n92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n92 OCA], [http://pdbe.org/4n92 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4n92 RCSB], [http://www.ebi.ac.uk/pdbsum/4n92 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4n92 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=4n92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n92 OCA], [http://pdbe.org/4n92 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4n92 RCSB], [http://www.ebi.ac.uk/pdbsum/4n92 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4n92 ProSAT]</span></td></tr>
Line 24:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Clostridium licheniforme weigmann 1898]]
	[[Category: Beta-lactamase]]		[[Category: Beta-lactamase]]
		+	[[Category: Large Structures]]
	[[Category: Pan, X]]		[[Category: Pan, X]]
	[[Category: Wong, W]]		[[Category: Wong, W]]
	[[Category: Zhao, Y]]		[[Category: Zhao, Y]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 17:45, 11 August 2016

OCA — Thu, 11 Aug 2016 17:45:51 GMT

←Older revision		Revision as of 17:45, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of beta-lactamse PenP_E166S==		==Crystal structure of beta-lactamse PenP_E166S==
	<StructureSection load='4n92' size='340' side='right' caption='[[4n92]], [[Resolution\|resolution]] 1.93Å' scene=''>		<StructureSection load='4n92' size='340' side='right' caption='[[4n92]], [[Resolution\|resolution]] 1.93Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4n9k\|4n9k]], [[4n9l\|4n9l]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4n9k\|4n9k]], [[4n9l\|4n9l]]</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='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=4n92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n92 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4n92 RCSB], [http://www.ebi.ac.uk/pdbsum/4n92 PDBsum]</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=4n92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n92 OCA], [http://pdbe.org/4n92 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4n92 RCSB], [http://www.ebi.ac.uk/pdbsum/4n92 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4n92 ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 15:		Line 16:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4n92" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta-lactamase\|Beta-lactamase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:45, 20 January 2015

OCA — Tue, 20 Jan 2015 07:45:46 GMT

←Older revision		Revision as of 07:45, 20 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4n92]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N92 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4N92 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4n92]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N92 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4N92 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4n9k\|4n9k]], [[4n9l\|4n9l]]</td></tr>	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4n9k\|4n9k]], [[4n9l\|4n9l]]</td></tr>
-	<tr><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='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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4n92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n92 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4n92 RCSB], [http://www.ebi.ac.uk/pdbsum/4n92 PDBsum]</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=4n92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n92 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4n92 RCSB], [http://www.ebi.ac.uk/pdbsum/4n92 PDBsum]</span></td></tr>
-	<table>	+	</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 20:
	</StructureSection>		</StructureSection>
	[[Category: Beta-lactamase]]		[[Category: Beta-lactamase]]
-	[[Category: Pan, X.]]	+	[[Category: Pan, X]]
-	[[Category: Wong, W.]]	+	[[Category: Wong, W]]
-	[[Category: Zhao, Y~~.]]~~	+	[[Category: Zhao, Y]]
-	~~[[Category: Beta-lactamase~~]]	+
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 09:55, 10 September 2014

OCA — Wed, 10 Sep 2014 09:55:40 GMT

←Older revision		Revision as of 09:55, 10 September 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Crystal structure of beta-lactamse PenP_E166S==
		+	<StructureSection load='4n92' size='340' side='right' caption='[[4n92]], [[Resolution\|resolution]] 1.93Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4n92]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N92 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4N92 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4n9k\|4n9k]], [[4n9l\|4n9l]]</td></tr>
		+	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4n92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n92 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4n92 RCSB], [http://www.ebi.ac.uk/pdbsum/4n92 PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Most class A beta-lactamases cannot hydrolyze carbapenem antibiotics effectively. The molecular mechanism of this catalytic inefficiency has been attributed to the unique stereochemistry of carbapenems, including their 6-alpha-hydroxyethyl side chain and the transition between two tautomeric states when bound at the active site. Previous studies have shown that the 6-alpha-hydroxyethyl side chain of carbapenems can interfere with catalysis by forming hydrogen bonds with the deacylation water molecule to reduce its nucleophilicity. Here our studies of a class A noncarbapenemase PenP demonstrate that substituting the general base residue Glu166 with Ser or other residues leads to a significant enhancement of the acylation kinetics by approximately 100-500 times toward carbapenems like meropenem. The structures of PenP and Glu166Ser both in apo form and in complex with meropenem reveal that Glu166 is critical for the formation of a hydrogen bonding network within the active site that locks Asn170 in an orientation to impose steric clash with the 6-alpha-hydroxyethyl side chain of meropenem. The Glu166Ser substitution weakens this network and enables Asn170 to adopt an alternative conformation to avoid steric clash and accommodate faster acylation kinetics. Furthermore, the weakened hydrogen bonding network caused by the Glu166Ser substitution allows the 6-alpha-hydroxyethyl moiety to adopt a catalytically favorable orientation as seen in class A carbapenemases. In summary, our data identify a previously unreported role of the universally conserved general base residue Glu166 in impeding the proper binding of carbapenems by restricting their 6-alpha-hydroxyethyl group.

-	~~The entry 4n92 is ON HOLD until Paper Publication~~	+	Perturbing the General Base Residue Glu166 in the Active Site of Class A beta-Lactamase Leads to Enhanced Carbapenem Binding and Acylation.,Pan X, Wong WT, He Y, Jiang Y, Zhao Y Biochemistry. 2014 Aug 26;53(33):5414-23. doi: 10.1021/bi401609h. Epub 2014 Aug, 15. PMID:25020031<ref>PMID:25020031</ref>

-	~~Authors~~: Pan, X., Wong, W., Zhao, Y.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Crystal structure of beta~~-~~lactamse PenP_E166S~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Beta-lactamase]]
		+	[[Category: Pan, X.]]
		+	[[Category: Wong, W.]]
		+	[[Category: Zhao, Y.]]
		+	[[Category: Beta-lactamase]]
		+	[[Category: Hydrolase]]

OCA at 07:50, 28 May 2014

OCA — Wed, 28 May 2014 07:50:03 GMT

←Older revision		Revision as of 07:50, 28 May 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4n92 is ON HOLD	+	The entry 4n92 is ON HOLD until Paper Publication

	Authors: Pan, X., Wong, W., Zhao, Y.		Authors: Pan, X., Wong, W., Zhao, Y.

	Description: Crystal structure of beta-lactamse PenP_E166S		Description: Crystal structure of beta-lactamse PenP_E166S

OCA at 06:47, 4 December 2013

OCA — Wed, 04 Dec 2013 06:47:32 GMT

←Older revision		Revision as of 06:47, 4 December 2013
Line 3:		Line 3:
	The entry 4n92 is ON HOLD		The entry 4n92 is ON HOLD

-	Authors: ~~Xuehua~~ Pan, ~~Waiting~~ Wong, ~~Yanxiang~~ Zhao	+	Authors: Pan, X., Wong, W., Zhao, Y.

-	Description: ~~crystal~~ structure of beta-lactamse PenP_E166S	+	Description: Crystal structure of beta-lactamse PenP_E166S

OCA: Protected "4n92" [edit=sysop:move=sysop]

OCA — Wed, 06 Nov 2013 07:04:13 GMT

Protected "4n92" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:04, 6 November 2013

OCA: New page: '''Unreleased structure''' The entry 4n92 is ON HOLD Authors: Xuehua Pan, Waiting Wong, Yanxiang Zhao Description: crystal structure of beta-lactamse PenP_E166S

OCA — Wed, 06 Nov 2013 07:04:12 GMT

New page: '''Unreleased structure''' The entry 4n92 is ON HOLD Authors: Xuehua Pan, Waiting Wong, Yanxiang Zhao Description: crystal structure of beta-lactamse PenP_E166S

New page

'''Unreleased structure'''

The entry 4n92 is ON HOLD

Authors: Xuehua Pan, Waiting Wong, Yanxiang Zhao

Description: crystal structure of beta-lactamse PenP_E166S