4euz - Revision history

OCA at 15:09, 14 March 2024

2024-03-14T15:09:52Z

← Older revision		Revision as of 15:09, 14 March 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4euz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Serratia_fonticola Serratia fonticola]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EUZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EUZ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4euz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Serratia_fonticola Serratia fonticola]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EUZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EUZ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HAR:N-OMEGA-HYDROXY-L-ARGININE'>HAR</scene>, <scene name='pdbligand=MEM:(4R,5S,6S)-3-{[(3S,5S)-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL}-6-[(1R)-1-HYDROXYETHYL]-4-METHYL-7-OXO-1-AZABICYCLO[3.2.0]HEPT-2-ENE-2-CARBOXYLIC+ACID'>MEM</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.08Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HAR:N-OMEGA-HYDROXY-L-ARGININE'>HAR</scene>, <scene name='pdbligand=MEM:(4R,5S,6S)-3-{[(3S,5S)-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL}-6-[(1R)-1-HYDROXYETHYL]-4-METHYL-7-OXO-1-AZABICYCLO[3.2.0]HEPT-2-ENE-2-CARBOXYLIC+ACID'>MEM</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=4euz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4euz OCA], [https://pdbe.org/4euz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4euz RCSB], [https://www.ebi.ac.uk/pdbsum/4euz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4euz 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=4euz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4euz OCA], [https://pdbe.org/4euz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4euz RCSB], [https://www.ebi.ac.uk/pdbsum/4euz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4euz ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/Q6JP75_SERFO Q6JP75_SERFO]		[https://www.uniprot.org/uniprot/Q6JP75_SERFO Q6JP75_SERFO]
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Carbapenems are the most potent beta-lactam antibiotics and key drugs for treating infections by Gram-negative bacteria. In such organisms, beta-lactam resistance arises principally from beta-lactamase production. Although carbapenems escape the activity of most beta-lactamases, due in the class A enzymes to slow deacylation of the covalent acylenzyme intermediate, carbapenem-hydrolyzing class A beta-lactamases are now disseminating in clinically relevant bacteria. The reasons why carbapenems are substrates for these enzymes, but inhibit other class A beta-lactamases, remain to be fully established. Here, we present crystal structures of the class A carbapenemase SFC-1 from Serratia fonticola and of complexes of its Ser70 Ala (Michaelis) and Glu166 Ala (acylenzyme) mutants with the carbapenem meropenem. These are the first crystal structures of carbapenem complexes of a class A carbapenemase. Our data reveal that, in the SFC-1 acylenzyme complex, the meropenem 6alpha-1R-hydroxyethyl group interacts with Asn132, but not with the deacylating water molecule. Molecular dynamics simulations indicate that this mode of binding occurs in both the Michaelis and acylenzyme complexes of wild-type SFC-1. In carbapenem-inhibited class A beta-lactamases, it is proposed that the deacylating water molecule is deactivated by interaction with the carbapenem 6alpha-1R-hydroxyethyl substituent. Structural comparisons with such enzymes suggest that in SFC-1 subtle repositioning of key residues (Ser70, Ser130, Asn132 and Asn170) enlarges the active site, permitting rotation of the carbapenem 6alpha-1R-hydroxyethyl group and abolishing this contact. Our data show that SFC-1, and by implication other such carbapenem-hydrolyzing enzymes, uses Asn132 to orient bound carbapenems for efficient deacylation and prevent their interaction with the deacylating water molecule.

	The basis for carbapenem hydrolysis by class A beta-lactamases: a combined investigation using crystallography and simulations.,Fonseca F, Chudyk EI, van der Kamp MW, Correia A, Mulholland AJ, Spencer J J Am Chem Soc. 2012 Nov 7;134(44):18275-85. doi: 10.1021/ja304460j. Epub 2012 Oct, 29. PMID:23030300<ref>PMID:23030300</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4euz" 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 04:17, 7 October 2022

2022-10-07T04:17:39Z

← Older revision		Revision as of 04:17, 7 October 2022
Line 1:		Line 1:

	==Crystal structure of serratia fonticola carbapenemase SFC-1 S70A-Meropenem complex==		==Crystal structure of serratia fonticola carbapenemase SFC-1 S70A-Meropenem complex==
	<StructureSection load='4euz' size='340' side='right' caption='[[4euz]], [[Resolution\|resolution]] 1.08Å' scene=''>		<StructureSection load='4euz' size='340' side='right'caption='[[4euz]], [[Resolution\|resolution]] 1.08Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4euz]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Atcc_29844 Atcc 29844~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EUZ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4EUZ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4euz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Serratia_fonticola Serratia fonticola]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EUZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EUZ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MEM:(4R,5S,6S)-3-{[(3S,5S)-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL}-6-[(1R)-1-HYDROXYETHYL]-4-METHYL-7-OXO-1-AZABICYCLO[3.2.0]HEPT-2-ENE-2-CARBOXYLIC+ACID'>MEM</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene~~></td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HAR:N-OMEGA-HYDROXY-L-ARGININE'>HAR</scene>, <scene name='pdbligand=MEM:(4R,5S,6S)-3-{[(3S,5S)-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL}-6-[(1R)-1-HYDROXYETHYL]-4-METHYL-7-OXO-1-AZABICYCLO[3.2.0]HEPT-2-ENE-2-CARBOXYLIC+ACID'>MEM</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HAR:N-OMEGA-HYDROXY-L-ARGININE'>HAR</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=4euz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4euz OCA], [https://pdbe.org/4euz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4euz RCSB], [https://www.ebi.ac.uk/pdbsum/4euz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4euz ProSAT]</span></td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4eqi\|4eqi]], [[4ev4\|4ev4]]</td></tr>~~
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BLASFC-1, SFC-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=47917 ATCC 29844])</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=4euz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4euz OCA], [~~http~~://pdbe.org/4euz PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4euz RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4euz PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4euz ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[https://www.uniprot.org/uniprot/Q6JP75_SERFO Q6JP75_SERFO]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 20:

	==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: ~~Atcc 29844~~]]		[[Category: Large Structures]]
	[[Category: ~~Beta-lactamase~~]]		[[Category: Serratia fonticola]]
	[[Category: Fonseca, F]]		[[Category: Fonseca F]]
	[[Category: Spencer, J]]		[[Category: Spencer J]]
	~~[[Category: Antibiotic resistance]]~~
	~~[[Category: Beta-lactamase complex]]~~
	~~[[Category: Carbapenemase]]~~
	~~[[Category: Hydrolase]]~~
	~~[[Category: Hydrolase-antibiotic complex~~]]

OCA at 09:47, 5 August 2016

2016-08-05T09:47:21Z

← Older revision		Revision as of 09:47, 5 August 2016
Line 1:		Line 1:

	==Crystal structure of serratia fonticola carbapenemase SFC-1 S70A-Meropenem complex==		==Crystal structure of serratia fonticola carbapenemase SFC-1 S70A-Meropenem complex==
	<StructureSection load='4euz' size='340' side='right' caption='[[4euz]], [[Resolution\|resolution]] 1.08Å' scene=''>		<StructureSection load='4euz' size='340' side='right' caption='[[4euz]], [[Resolution\|resolution]] 1.08Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4euz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Serratia_fonticola Serratia fonticola~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EUZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EUZ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4euz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_29844 Atcc 29844]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EUZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EUZ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MEM:(4R,5S,6S)-3-{[(3S,5S)-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL}-6-[(1R)-1-HYDROXYETHYL]-4-METHYL-7-OXO-1-AZABICYCLO[3.2.0]HEPT-2-ENE-2-CARBOXYLIC+ACID'>MEM</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MEM:(4R,5S,6S)-3-{[(3S,5S)-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL}-6-[(1R)-1-HYDROXYETHYL]-4-METHYL-7-OXO-1-AZABICYCLO[3.2.0]HEPT-2-ENE-2-CARBOXYLIC+ACID'>MEM</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HAR:N-OMEGA-HYDROXY-L-ARGININE'>HAR</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HAR:N-OMEGA-HYDROXY-L-ARGININE'>HAR</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4eqi\|4eqi]], [[4ev4\|4ev4]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4eqi\|4eqi]], [[4ev4\|4ev4]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BLASFC-1, SFC-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=47917 ~~Serratia fonticola~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BLASFC-1, SFC-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=47917 ATCC 29844])</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=4euz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4euz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4euz RCSB], [http://www.ebi.ac.uk/pdbsum/4euz 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=4euz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4euz OCA], [http://pdbe.org/4euz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4euz RCSB], [http://www.ebi.ac.uk/pdbsum/4euz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4euz ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 18:		Line 19:
	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 4euz" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Atcc 29844]]
	[[Category: Beta-lactamase]]		[[Category: Beta-lactamase]]
	~~[[Category: Serratia fonticola]]~~
	[[Category: Fonseca, F]]		[[Category: Fonseca, F]]
	[[Category: Spencer, J]]		[[Category: Spencer, J]]

OCA at 11:15, 21 December 2014

2014-12-21T11:15:30Z

← Older revision		Revision as of 11:15, 21 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_4euz\| PDB=4euz \| SCENE= }}~~		==Crystal structure of serratia fonticola carbapenemase SFC-1 S70A-Meropenem complex==
	===Crystal structure of serratia fonticola carbapenemase SFC-1 S70A-Meropenem complex===		<StructureSection load='4euz' size='340' side='right' caption='[[4euz]], [[Resolution\|resolution]] 1.08Å' scene=''>
	{~~{ABSTRACT_PUBMED_23030300}~~}		== Structural highlights ==
			<table><tr><td colspan='2'>[[4euz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Serratia_fonticola Serratia fonticola]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EUZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EUZ FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MEM:(4R,5S,6S)-3-{[(3S,5S)-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL}-6-[(1R)-1-HYDROXYETHYL]-4-METHYL-7-OXO-1-AZABICYCLO[3.2.0]HEPT-2-ENE-2-CARBOXYLIC+ACID'>MEM</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
			<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HAR:N-OMEGA-HYDROXY-L-ARGININE'>HAR</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4eqi\|4eqi]], [[4ev4\|4ev4]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BLASFC-1, SFC-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=47917 Serratia fonticola])</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=4euz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4euz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4euz RCSB], [http://www.ebi.ac.uk/pdbsum/4euz PDBsum]</span></td></tr>
			</table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Carbapenems are the most potent beta-lactam antibiotics and key drugs for treating infections by Gram-negative bacteria. In such organisms, beta-lactam resistance arises principally from beta-lactamase production. Although carbapenems escape the activity of most beta-lactamases, due in the class A enzymes to slow deacylation of the covalent acylenzyme intermediate, carbapenem-hydrolyzing class A beta-lactamases are now disseminating in clinically relevant bacteria. The reasons why carbapenems are substrates for these enzymes, but inhibit other class A beta-lactamases, remain to be fully established. Here, we present crystal structures of the class A carbapenemase SFC-1 from Serratia fonticola and of complexes of its Ser70 Ala (Michaelis) and Glu166 Ala (acylenzyme) mutants with the carbapenem meropenem. These are the first crystal structures of carbapenem complexes of a class A carbapenemase. Our data reveal that, in the SFC-1 acylenzyme complex, the meropenem 6alpha-1R-hydroxyethyl group interacts with Asn132, but not with the deacylating water molecule. Molecular dynamics simulations indicate that this mode of binding occurs in both the Michaelis and acylenzyme complexes of wild-type SFC-1. In carbapenem-inhibited class A beta-lactamases, it is proposed that the deacylating water molecule is deactivated by interaction with the carbapenem 6alpha-1R-hydroxyethyl substituent. Structural comparisons with such enzymes suggest that in SFC-1 subtle repositioning of key residues (Ser70, Ser130, Asn132 and Asn170) enlarges the active site, permitting rotation of the carbapenem 6alpha-1R-hydroxyethyl group and abolishing this contact. Our data show that SFC-1, and by implication other such carbapenem-hydrolyzing enzymes, uses Asn132 to orient bound carbapenems for efficient deacylation and prevent their interaction with the deacylating water molecule.

	~~==About this Structure==~~		The basis for carbapenem hydrolysis by class A beta-lactamases: a combined investigation using crystallography and simulations.,Fonseca F, Chudyk EI, van der Kamp MW, Correia A, Mulholland AJ, Spencer J J Am Chem Soc. 2012 Nov 7;134(44):18275-85. doi: 10.1021/ja304460j. Epub 2012 Oct, 29. PMID:23030300<ref>PMID:23030300</ref>
	~~[[4euz]] is~~ a ~~1 chain structure with sequence from [http~~:~~//en~~.~~wikipedia~~.~~org~~/~~wiki/Serratia_fonticola Serratia fonticola]~~. ~~Full crystallographic information is available from [http~~://~~oca~~.~~weizmann~~.ac.~~il/oca-bin~~/~~ocashort?id=4EUZ OCA].~~
			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>

	==See Also==		==See Also==
	*[[Beta-lactamase\|Beta-lactamase]]		*[[Beta-lactamase\|Beta-lactamase]]
			== References ==
	==~~Reference~~==		<references/>
	~~<ref group="xtra">PMID:023030300</ref>~~<references ~~group="xtra"~~/><~~references~~/>		__TOC__
			</StructureSection>
	[[Category: Beta-lactamase]]		[[Category: Beta-lactamase]]
	[[Category: Serratia fonticola]]		[[Category: Serratia fonticola]]
	[[Category: Fonseca, F.]]		[[Category: Fonseca, F]]
	[[Category: Spencer, J.]]		[[Category: Spencer, J]]
	[[Category: Antibiotic resistance]]		[[Category: Antibiotic resistance]]
	[[Category: Beta-lactamase complex]]		[[Category: Beta-lactamase complex]]

OCA at 06:01, 28 August 2013

2013-08-28T06:01:49Z

← Older revision		Revision as of 06:01, 28 August 2013
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	~~[[Image:4euz.jpg\|left\|200px]]~~

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_4euz", creates the "Structure Box" on the page.~~
	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display.~~
	~~-->~~
	{{STRUCTURE_4euz\| PDB=4euz \| SCENE= }}		{{STRUCTURE_4euz\| PDB=4euz \| SCENE= }}

	===Crystal structure of serratia fonticola carbapenemase SFC-1 S70A-Meropenem complex===		===Crystal structure of serratia fonticola carbapenemase SFC-1 S70A-Meropenem complex===
			{{ABSTRACT_PUBMED_23030300}}

	==About this Structure==		==About this Structure==
	[[4euz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Serratia_fonticola Serratia fonticola]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EUZ OCA].		[[4euz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Serratia_fonticola Serratia fonticola]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EUZ OCA].

			==See Also==
			*[[Beta-lactamase\|Beta-lactamase]]

			==Reference==
			<ref group="xtra">PMID:023030300</ref><references group="xtra"/><references/>
	[[Category: Beta-lactamase]]		[[Category: Beta-lactamase]]
	[[Category: Serratia fonticola]]		[[Category: Serratia fonticola]]

OCA at 06:18, 23 May 2012

2012-05-23T06:18:38Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:4euz.jpg|left|200px]]
-The entry 4euz is ON HOLD
+<!--
-Authors: Fonseca, F., Spencer, J.
+===Crystal structure of serratia fonticola carbapenemase SFC-1 S70A-Meropenem complex===
-Description: Crystal structure of serratia fonticola carbapenemase SFC-1 S70A-Meropenem complex

OCA at 08:50, 9 May 2012

2012-05-09T08:50:34Z

← Older revision		Revision as of 08:50, 9 May 2012
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	Authors: Fonseca, F., Spencer, J.		Authors: Fonseca, F., Spencer, J.

	Description: ~~CRYSTAL STRUCTURE OF SERRATIA FONTICOLA CARBAPENEMASE~~ SFC-1 S70A-~~MEROPENEM COMPLEX~~		Description: Crystal structure of serratia fonticola carbapenemase SFC-1 S70A-Meropenem complex

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

2012-05-02T19:00:28Z

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

← Older revision	Revision as of 19:00, 2 May 2012
(No difference)

OCA: New page: '''Unreleased structure''' The entry 4euz is ON HOLD Authors: Fonseca, F., Spencer, J. Description: CRYSTAL STRUCTURE OF SERRATIA FONTICOLA CARBAPENEMASE SFC-1 S70A-MEROPENEM COMPLEX

2012-05-02T19:00:27Z

New page: '''Unreleased structure''' The entry 4euz is ON HOLD Authors: Fonseca, F., Spencer, J. Description: CRYSTAL STRUCTURE OF SERRATIA FONTICOLA CARBAPENEMASE SFC-1 S70A-MEROPENEM COMPLEX

New page

'''Unreleased structure'''

The entry 4euz is ON HOLD

Authors: Fonseca, F., Spencer, J.

Description: CRYSTAL STRUCTURE OF SERRATIA FONTICOLA CARBAPENEMASE SFC-1 S70A-MEROPENEM COMPLEX