4dds - Revision history

OCA at 08:18, 9 October 2024

2024-10-09T08:18:21Z

← Older revision		Revision as of 08:18, 9 October 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/Q9L5C8_ECOLX Q9L5C8_ECOLX]		[https://www.uniprot.org/uniprot/Q9L5C8_ECOLX Q9L5C8_ECOLX]
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The emergence of CTX-M class A extended-spectrum beta-lactamases poses a serious health threat to the public. We have applied structure-based design to improve the potency of a novel noncovalent tetrazole-containing CTX-M inhibitor (K(i) = 21 muM) more than 200-fold via structural modifications targeting two binding hot spots, a hydrophobic shelf formed by Pro167 and a polar site anchored by Asp240. Functional groups contacting each binding hot spot independently in initial designs were later combined to produce analogues with submicromolar potencies, including 6-trifluoromethyl-3H-benzoimidazole-4-carboxylic acid [3-(1H-tetrazol-5-yl)-phenyl]-amide, which had a K(i) value of 89 nM and reduced the MIC of cefotaxime by 64-fold in CTX-M-9 expressing Escherichia coli . The in vitro potency gains were accompanied by improvements in ligand efficiency (from 0.30 to 0.39) and LipE (from 1.37 to 3.86). These new analogues represent the first nM-affinity noncovalent inhibitors of a class A beta-lactamase. Their complex crystal structures provide valuable information about ligand binding for future inhibitor design.

			Structure-Based Design of Potent and Ligand-Efficient Inhibitors of CTX-M Class A beta-Lactamase.,Nichols DA, Jaishankar P, Larson W, Smith E, Liu G, Beyrouthy R, Bonnet R, Renslo AR, Chen Y J Med Chem. 2012 Mar 8;55(5):2163-72. Epub 2012 Feb 14. PMID:22296601<ref>PMID:22296601</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 4dds" 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 14:32, 14 March 2024

2024-03-14T14:32:47Z

← Older revision		Revision as of 14:32, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4dds]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DDS FirstGlance]. <br>		<table><tr><td colspan='2'>[[4dds]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DDS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0J7:3-(PYRIMIDIN-2-YL)-N-[3-(1H-TETRAZOL-5-YL)PHENYL]BENZAMIDE'>0J7</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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]] 1.36Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0J7:3-(PYRIMIDIN-2-YL)-N-[3-(1H-TETRAZOL-5-YL)PHENYL]BENZAMIDE'>0J7</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=4dds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dds OCA], [https://pdbe.org/4dds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dds RCSB], [https://www.ebi.ac.uk/pdbsum/4dds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dds 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=4dds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dds OCA], [https://pdbe.org/4dds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dds RCSB], [https://www.ebi.ac.uk/pdbsum/4dds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dds ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/Q9L5C8_ECOLX Q9L5C8_ECOLX]]		[https://www.uniprot.org/uniprot/Q9L5C8_ECOLX Q9L5C8_ECOLX]
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	The emergence of CTX-M class A extended-spectrum beta-lactamases poses a serious health threat to the public. We have applied structure-based design to improve the potency of a novel noncovalent tetrazole-containing CTX-M inhibitor (K(i) = 21 muM) more than 200-fold via structural modifications targeting two binding hot spots, a hydrophobic shelf formed by Pro167 and a polar site anchored by Asp240. Functional groups contacting each binding hot spot independently in initial designs were later combined to produce analogues with submicromolar potencies, including 6-trifluoromethyl-3H-benzoimidazole-4-carboxylic acid [3-(1H-tetrazol-5-yl)-phenyl]-amide, which had a K(i) value of 89 nM and reduced the MIC of cefotaxime by 64-fold in CTX-M-9 expressing Escherichia coli . The in vitro potency gains were accompanied by improvements in ligand efficiency (from 0.30 to 0.39) and LipE (from 1.37 to 3.86). These new analogues represent the first nM-affinity noncovalent inhibitors of a class A beta-lactamase. Their complex crystal structures provide valuable information about ligand binding for future inhibitor design.

	Structure-Based Design of Potent and Ligand-Efficient Inhibitors of CTX-M Class A beta-Lactamase.,Nichols DA, Jaishankar P, Larson W, Smith E, Liu G, Beyrouthy R, Bonnet R, Renslo AR, Chen Y J Med Chem. 2012 Mar 8;55(5):2163-72. Epub 2012 Feb 14. PMID:22296601<ref>PMID:22296601</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4dds" 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 08:13, 21 September 2022

2022-09-21T08:13:38Z

← Older revision		Revision as of 08:13, 21 September 2022
Line 1:		Line 1:

	==CTX-M-9 class A beta-lactamase complexed with compound 11==		==CTX-M-9 class A beta-lactamase complexed with compound 11==
	<StructureSection load='4dds' size='340' side='right' caption='[[4dds]], [[Resolution\|resolution]] 1.36Å' scene=''>		<StructureSection load='4dds' size='340' side='right'caption='[[4dds]], [[Resolution\|resolution]] 1.36Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4dds]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"bacillus_coli"_migula_1895 "bacillus~~ coli~~" migula 1895~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DDS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4DDS FirstGlance]. <br>		<table><tr><td colspan='2'>[[4dds]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DDS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0J7:3-(PYRIMIDIN-2-YL)-N-[3-(1H-TETRAZOL-5-YL)PHENYL]BENZAMIDE'>0J7</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>~~</td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0J7:3-(PYRIMIDIN-2-YL)-N-[3-(1H-TETRAZOL-5-YL)PHENYL]BENZAMIDE'>0J7</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr>
	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=4dds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dds OCA], [https://pdbe.org/4dds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dds RCSB], [https://www.ebi.ac.uk/pdbsum/4dds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dds ProSAT]</span></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3g2y\|3g2y]], [[3g2z\|3g2z]], [[3g30\|3g30]], [[3g31\|3g31]], [[3g32\|3g32]], [[3g35\|3g35]], [[4ddy\|4ddy]], [[4de0\|4de0]], [[4de1\|4de1]], [[4de2\|4de2]], [[4de3\|4de3]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">blaCTX-M-9, blaCTX-M-9a, blaCTX-M-9b, CTX-M ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=4dds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dds OCA], [~~http~~://pdbe.org/4dds PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4dds RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4dds PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4dds ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[[https://www.uniprot.org/uniprot/Q9L5C8_ECOLX Q9L5C8_ECOLX]]
	<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: ~~Bacillus~~ coli ~~migula 1895~~]]		[[Category: Escherichia coli]]
	[[Category: ~~Beta-lactamase~~]]		[[Category: Large Structures]]
	[[Category: Chen, Y]]		[[Category: Chen Y]]
	[[Category: Nichols~~, D A]]~~		[[Category: Nichols DA]]
	~~[[Category: Ctx-m]]~~
	~~[[Category: Fragment]]~~
	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~
	~~[[Category: Molecular docking~~]]

OCA at 02:46, 11 December 2016

2016-12-11T02:46:55Z

← Older revision		Revision as of 02:46, 11 December 2016
Line 1:		Line 1:

	==CTX-M-9 class A beta-lactamase complexed with compound 11==		==CTX-M-9 class A beta-lactamase complexed with compound 11==
	<StructureSection load='4dds' size='340' side='right' caption='[[4dds]], [[Resolution\|resolution]] 1.36Å' scene=''>		<StructureSection load='4dds' size='340' side='right' caption='[[4dds]], [[Resolution\|resolution]] 1.36Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4dds]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Escherichia_coli Escherichia~~ coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DDS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DDS FirstGlance]. <br>		<table><tr><td colspan='2'>[[4dds]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DDS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DDS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0J7:3-(PYRIMIDIN-2-YL)-N-[3-(1H-TETRAZOL-5-YL)PHENYL]BENZAMIDE'>0J7</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0J7:3-(PYRIMIDIN-2-YL)-N-[3-(1H-TETRAZOL-5-YL)PHENYL]BENZAMIDE'>0J7</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3g2y\|3g2y]], [[3g2z\|3g2z]], [[3g30\|3g30]], [[3g31\|3g31]], [[3g32\|3g32]], [[3g35\|3g35]], [[4ddy\|4ddy]], [[4de0\|4de0]], [[4de1\|4de1]], [[4de2\|4de2]], [[4de3\|4de3]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3g2y\|3g2y]], [[3g2z\|3g2z]], [[3g30\|3g30]], [[3g31\|3g31]], [[3g32\|3g32]], [[3g35\|3g35]], [[4ddy\|4ddy]], [[4de0\|4de0]], [[4de1\|4de1]], [[4de2\|4de2]], [[4de3\|4de3]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">blaCTX-M-9, blaCTX-M-9a, blaCTX-M-9b, CTX-M ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 ~~Escherichia~~ coli])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">blaCTX-M-9, blaCTX-M-9a, blaCTX-M-9b, CTX-M ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=4dds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dds OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dds RCSB], [http://www.ebi.ac.uk/pdbsum/4dds 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=4dds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dds OCA], [http://pdbe.org/4dds PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dds RCSB], [http://www.ebi.ac.uk/pdbsum/4dds PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dds 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 4dds" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Bacillus coli migula 1895]]
	[[Category: Beta-lactamase]]		[[Category: Beta-lactamase]]
	~~[[Category: Escherichia coli]]~~
	[[Category: Chen, Y]]		[[Category: Chen, Y]]
	[[Category: Nichols, D A]]		[[Category: Nichols, D A]]

OCA at 14:55, 9 December 2014

2014-12-09T14:55:29Z

← Older revision		Revision as of 14:55, 9 December 2014
Line 1:		Line 1:
	[[~~Image~~:~~4dds~~.~~png~~\|~~left~~\|~~200px~~]]		==CTX-M-9 class A beta-lactamase complexed with compound 11==
			<StructureSection load='4dds' size='340' side='right' caption='[[4dds]], [[Resolution\|resolution]] 1.36Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[4dds]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DDS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DDS FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0J7:3-(PYRIMIDIN-2-YL)-N-[3-(1H-TETRAZOL-5-YL)PHENYL]BENZAMIDE'>0J7</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>
			<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3g2y\|3g2y]], [[3g2z\|3g2z]], [[3g30\|3g30]], [[3g31\|3g31]], [[3g32\|3g32]], [[3g35\|3g35]], [[4ddy\|4ddy]], [[4de0\|4de0]], [[4de1\|4de1]], [[4de2\|4de2]], [[4de3\|4de3]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">blaCTX-M-9, blaCTX-M-9a, blaCTX-M-9b, CTX-M ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])</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=4dds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dds OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dds RCSB], [http://www.ebi.ac.uk/pdbsum/4dds PDBsum]</span></td></tr>
			</table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The emergence of CTX-M class A extended-spectrum beta-lactamases poses a serious health threat to the public. We have applied structure-based design to improve the potency of a novel noncovalent tetrazole-containing CTX-M inhibitor (K(i) = 21 muM) more than 200-fold via structural modifications targeting two binding hot spots, a hydrophobic shelf formed by Pro167 and a polar site anchored by Asp240. Functional groups contacting each binding hot spot independently in initial designs were later combined to produce analogues with submicromolar potencies, including 6-trifluoromethyl-3H-benzoimidazole-4-carboxylic acid [3-(1H-tetrazol-5-yl)-phenyl]-amide, which had a K(i) value of 89 nM and reduced the MIC of cefotaxime by 64-fold in CTX-M-9 expressing Escherichia coli . The in vitro potency gains were accompanied by improvements in ligand efficiency (from 0.30 to 0.39) and LipE (from 1.37 to 3.86). These new analogues represent the first nM-affinity noncovalent inhibitors of a class A beta-lactamase. Their complex crystal structures provide valuable information about ligand binding for future inhibitor design.

	~~{{STRUCTURE_4dds\| PDB=4dds \| SCENE= }}~~		Structure-Based Design of Potent and Ligand-Efficient Inhibitors of CTX-M Class A beta-Lactamase.,Nichols DA, Jaishankar P, Larson W, Smith E, Liu G, Beyrouthy R, Bonnet R, Renslo AR, Chen Y J Med Chem. 2012 Mar 8;55(5):2163-72. Epub 2012 Feb 14. PMID:22296601<ref>PMID:22296601</ref>

	~~===CTX-M-9 class A beta-lactamase complexed with compound 11===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
	~~{{ABSTRACT_PUBMED_22296601}}~~

	~~==About this Structure==~~
	~~[[4dds]] is~~ a ~~2 chain structure with sequence from [http://en.wikipedia~~.~~org/wiki/Escherichia_coli Escherichia coli]~~. ~~Full crystallographic information is available from [http://oca~~.~~weizmann.ac.il/oca-bin~~/~~ocashort?id=4DDS OCA].~~

	==See Also==		==See Also==
	*[[Beta-lactamase\|Beta-lactamase]]		*[[Beta-lactamase\|Beta-lactamase]]
			== References ==
	==~~Reference~~==		<references/>
	<~~ref group="xtra">PMID:022296601<~~/~~ref~~><~~references group="xtra"~~/>		__TOC__
			</StructureSection>
	[[Category: Beta-lactamase]]		[[Category: Beta-lactamase]]
	[[Category: Escherichia coli]]		[[Category: Escherichia coli]]
	[[Category: Chen, Y.]]		[[Category: Chen, Y]]
	[[Category: Nichols, D A.]]		[[Category: Nichols, D A]]
	[[Category: Ctx-m]]		[[Category: Ctx-m]]
	[[Category: Fragment]]		[[Category: Fragment]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]
	[[Category: Molecular docking]]		[[Category: Molecular docking]]

OCA at 12:51, 20 October 2012

2012-10-20T12:51:28Z

← Older revision		Revision as of 12:51, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
	[[4dds]] is a 2 chain structure ~~of [[Beta-lactamase]]~~ with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DDS OCA].		[[4dds]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DDS OCA].

	==See Also==		==See Also==

OCA at 10:06, 26 July 2012

2012-07-26T10:06:22Z

← Older revision		Revision as of 10:06, 26 July 2012
Line 1:		Line 1:
	[[Image:4dds.~~jpg~~\|left\|200px]]		[[Image:4dds.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_4dds", 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_4dds\| PDB=4dds \| SCENE= }}		{{STRUCTURE_4dds\| PDB=4dds \| SCENE= }}

	===CTX-M-9 class A beta-lactamase complexed with compound 11===		===CTX-M-9 class A beta-lactamase complexed with compound 11===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_22296601}}, adds the Publication Abstract to the page~~
	~~(as it appears on PubMed at http://www.pubmed.gov), where 22296601 is the PubMed ID number.~~
	~~-->~~
	{{ABSTRACT_PUBMED_22296601}}		{{ABSTRACT_PUBMED_22296601}}

	==About this Structure==		==About this Structure==
	[[4dds]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DDS OCA].		[[4dds]] is a 2 chain structure of [[Beta-lactamase]] with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DDS OCA].

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

	==Reference==		==Reference==

OCA at 07:42, 28 March 2012

2012-03-28T07:42:09Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:4dds.jpg|left|200px]]
-The entry 4dds is ON HOLD  until Paper Publication
+<!--
-Authors: Nichols, D.A., Chen, Y.
+===CTX-M-9 class A beta-lactamase complexed with compound 11===
-Description: CTX-M-9 class A beta-lactamase complexed with compound 11

OCA at 07:00, 1 February 2012

2012-02-01T07:00:53Z

← Older revision		Revision as of 07:00, 1 February 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4dds is ON HOLD		The entry 4dds is ON HOLD until Paper Publication

	Authors: Nichols, D.A., Chen, Y.		Authors: Nichols, D.A., Chen, Y.

	Description: CTX-M-9 class A beta-lactamase complexed with compound 11		Description: CTX-M-9 class A beta-lactamase complexed with compound 11

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

2012-01-25T06:13:02Z

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

← Older revision	Revision as of 06:13, 25 January 2012
(No difference)