6ex7 - Revision history

OCA at 12:22, 9 May 2024

OCA — Thu, 09 May 2024 12:22:22 GMT

←Older revision		Revision as of 12:22, 9 May 2024
Line 1:		Line 1:

	==Crystal structure of NDM-1 metallo-beta-lactamase in complex with Cd ions and a hydrolyzed beta-lactam ligand - new refinement==		==Crystal structure of NDM-1 metallo-beta-lactamase in complex with Cd ions and a hydrolyzed beta-lactam ligand - new refinement==
-	<StructureSection load='6ex7' size='340' side='right' caption='[[6ex7]], [[Resolution\|resolution]] 1.95Å' scene=''>	+	<StructureSection load='6ex7' size='340' side='right'caption='[[6ex7]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ex7]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"bacillus_pneumoniae"_(schroeter_1886)_flugge_1886 "bacillus~~ pneumoniae~~" (schroeter 1886) flugge 1886~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EX7 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6EX7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ex7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EX7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EX7 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=TOE:2-[2-(2-METHOXY-ETHOXY)-ETHOXY]-ETHOXYL'>TOE</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</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]] 1.95Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hky\|4hky]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=TOE:2-[2-(2-METHOXY-ETHOXY)-ETHOXY]-ETHOXYL'>TOE</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">blaNDM-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=573 "Bacillus pneumoniae" (Schroeter 1886) Flugge 1886])</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=6ex7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ex7 OCA], [https://pdbe.org/6ex7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ex7 RCSB], [https://www.ebi.ac.uk/pdbsum/6ex7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ex7 ProSAT]</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=6ex7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ex7 OCA], [~~http~~://pdbe.org/6ex7 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6ex7 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6ex7 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6ex7 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/BLAN1_KLEPN BLAN1_KLEPN]] Confers resistance to many beta-lactam antibiotics, including some carbapenems. Does not confer resistance to the polymixin colistin or the fluoroquinolone ciprofloxacin.	+	[https://www.uniprot.org/uniprot/BLAN1_KLEPN BLAN1_KLEPN] Confers resistance to many beta-lactam antibiotics, including some carbapenems. Does not confer resistance to the polymixin colistin or the fluoroquinolone ciprofloxacin.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 21:

	==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: ~~Beta-lactamase~~]]	+	[[Category: Klebsiella pneumoniae]]
-	[[Category: Babnigg, J]]	+	[[Category: Large Structures]]
-	[[Category: Jaskolski, M]]	+	[[Category: Babnigg J]]
-	[[Category: Jedrzejczak, R]]	+	[[Category: Jaskolski M]]
-	[[Category: Joachimiak, A]]	+	[[Category: Jedrzejczak R]]
-	[[Category: Kim, Y]]	+	[[Category: Joachimiak A]]
-	[[Category: Minor, W]]	+	[[Category: Kim Y]]
-	[[Category: Mire, J]]	+	[[Category: Minor W]]
-	[[Category: Raczynska~~, J E~~]]	+	[[Category: Mire J]]
-	[[Category: Sacchettini, J]]	+	[[Category: Raczynska JE]]
-	[[Category: Shabalin~~, I G~~]]	+	[[Category: Sacchettini J]]
-	[[Category: Tesar, C]]	+	[[Category: Shabalin IG]]
-	[[Category: Wlodawer, A]]	+	[[Category: Tesar C]]
-	~~[[Category: Hydrolase]]~~	+	[[Category: Wlodawer A]]
-	~~[[Category: Metallo-beta-lactamase]]~~	+
-	~~[[Category: Ndm-1~~]]	+

OCA at 08:39, 26 December 2018

OCA — Wed, 26 Dec 2018 08:39:15 GMT

←Older revision		Revision as of 08:39, 26 December 2018
Line 14:		Line 14:
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	~~The specter~~ of ~~a return to an era in which infectious disease looms as a significant threat to human health is not just hyperbole; there are serious concerns about~~ the ~~widespread overuse and misuse~~ of antibiotics ~~contributing to increased~~ antibiotic resistance ~~in pathogens~~. ~~The recent discovery of a new enzyme, first identified in Klebsiella pneumoniae from a patient from New Delhi and denoted as NDM~~-1, ~~represents~~ an ~~example of extreme promiscuity: It hydrolyzes and inactivates nearly~~ all ~~known~~ beta-~~lactam~~-~~based~~ antibiotics ~~with startling efficiency~~. ~~NDM~~-~~1 can utilize different metal cofactors~~ and ~~seems to exploit~~ an ~~alternative mechanism based on~~ the ~~reaction conditions~~. ~~Here we report~~ the ~~results~~ of ~~a combined experimental and theoretical study~~ that ~~examines~~ the ~~substrate, metal binding,~~ and ~~catalytic mechanism~~ of the ~~enzyme~~. We ~~utilize~~ structures ~~obtained through X~~-~~ray crystallography~~, ~~biochemical assays~~, ~~and numerical simulation to construct~~ a ~~model~~ of the ~~enzyme catalytic pathway. The NDM-1 enzyme interacts with~~ the ~~substrate solely through zinc~~, or ~~other metals~~, ~~bound~~ in the ~~active site~~, ~~explaining~~ the ~~observed lack~~ of ~~specificity against a broad range~~ of ~~beta-lactam antibiotic agents~~. ~~The zinc ions also serve~~ to ~~activate a water molecule that hydrolyzes~~ the ~~beta-lactam ring through a proton shuttle~~.	+	beta-Lactamases are hydrolytic enzymes capable of opening the beta-lactam ring of antibiotics such as penicillin, thus endowing the bacteria that produce them with antibiotic resistance. Of particular medical concern are metallo-beta-lactamases (MBLs), with an active site built around coordinated Zn cations. MBLs are pan-reactive enzymes that can break down almost all classes of beta-lactams, including such last-resort antibiotics as carbapenems. They are not only broad-spectrum-reactive but are often plasmid-borne (e.g., the New Delhi enzyme, NDM), and can spread horizontally even among unrelated bacteria. Acquired MBLs are encoded by mobile genetic elements, which often include other resistance genes, making the microbiological situation particularly alarming. There is an urgent need to develop MBL inhibitors in order to rescue our antibiotic armory. A number of such efforts have been undertaken, most notably using the 3D structures of various MBLs as drug-design targets. Structure-guided drug discovery depends on the quality of the structures that are collected in the Protein Data Bank (PDB) and on the consistency of the information in dedicated beta-lactamase databases. We conducted a careful review of the crystal structures of class B beta-lactamases, concluding that the quality of these structures varies widely, especially in the regions where small molecules interact with the macromolecules. In a number of examples the interpretation of the bound ligands (e.g., inhibitors, substrate/product analogs) is doubtful or even incorrect, and it appears that in some cases the modeling of ligands was not supported by electron density. For ten MBL structures, alternative interpretations of the original diffraction data could be proposed and the new models have been deposited in the PDB. In four cases, these models, prepared jointly with the authors of the original depositions, superseded the previous deposits. This review emphasizes the importance of critical assessment of structural models describing key drug design targets at the level of the raw experimental data. Since the structures reviewed here are the basis for ongoing design of new MBL inhibitors, it is important to identify and correct the problems with ambiguous crystallographic interpretations, thus enhancing reproducibility in this highly medically relevant area.

-	~~NDM-1, the ultimate promiscuous enzyme: substrate recognition~~ and ~~catalytic mechanism~~.,~~Kim Y~~, ~~Cunningham MA~~, ~~Mire J~~, ~~Tesar C, Sacchettini J, Joachimiak~~ A ~~FASEB J~~. ~~2013 May~~;~~27(5)~~:~~1917~~-27. doi: 10.~~1096~~/fj.~~12-224014~~. Epub ~~2013 Jan 30~~. PMID:~~23363572~~<ref>PMID:~~23363572~~</ref>	+	A close look onto structural models and primary ligands of metallo-beta-lactamases.,Raczynska JE, Shabalin IG, Minor W, Wlodawer A, Jaskolski M Drug Resist Updat. 2018 Sep;40:1-12. doi: 10.1016/j.drup.2018.08.001. Epub 2018, Aug 25. PMID:30466711<ref>PMID:30466711</ref>

	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>

OCA at 06:07, 25 April 2018

OCA — Wed, 25 Apr 2018 06:07:54 GMT

←Older revision		Revision as of 06:07, 25 April 2018
Line 3:		Line 3:
	<StructureSection load='6ex7' size='340' side='right' caption='[[6ex7]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='6ex7' size='340' side='right' caption='[[6ex7]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ex7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EX7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ex7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_pneumoniae"_(schroeter_1886)_flugge_1886 "bacillus pneumoniae" (schroeter 1886) flugge 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EX7 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=TOE:2-[2-(2-METHOXY-ETHOXY)-ETHOXY]-ETHOXYL'>TOE</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=TOE:2-[2-(2-METHOXY-ETHOXY)-ETHOXY]-ETHOXYL'>TOE</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hky\|4hky]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hky\|4hky]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">blaNDM-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=573 "Bacillus pneumoniae" (Schroeter 1886) Flugge 1886])</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=6ex7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ex7 OCA], [http://pdbe.org/6ex7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ex7 RCSB], [http://www.ebi.ac.uk/pdbsum/6ex7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ex7 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=6ex7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ex7 OCA], [http://pdbe.org/6ex7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ex7 RCSB], [http://www.ebi.ac.uk/pdbsum/6ex7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ex7 ProSAT]</span></td></tr>
Line 13:		Line 14:
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	~~Resistance~~ to ~~beta-lactam~~ antibiotics ~~can be mediated by metallo~~-beta-~~lactamase enzymes (MBLs)~~. ~~An MBL inhibitor could restore the effectiveness of beta~~-~~lactams~~. We report on the ~~evaluation~~ of ~~approved thiol~~-~~containing drugs as inhibitors~~ of NDM-1, ~~VIM-1~~, ~~and IMP~~-7. ~~Drugs were assessed by a novel assay using~~ a ~~purchasable fluorescent substrate and thermal shift. Best compounds were tested in antimicrobial susceptibility assay. Using these orthogonal screening methods, we identified drugs~~ that ~~restored~~ the ~~activity of imipenem~~.	+	The specter of a return to an era in which infectious disease looms as a significant threat to human health is not just hyperbole; there are serious concerns about the widespread overuse and misuse of antibiotics contributing to increased antibiotic resistance in pathogens. The recent discovery of a new enzyme, first identified in Klebsiella pneumoniae from a patient from New Delhi and denoted as NDM-1, represents an example of extreme promiscuity: It hydrolyzes and inactivates nearly all known beta-lactam-based antibiotics with startling efficiency. NDM-1 can utilize different metal cofactors and seems to exploit an alternative mechanism based on the reaction conditions. Here we report the results of a combined experimental and theoretical study that examines the substrate, metal binding, and catalytic mechanism of the enzyme. We utilize structures obtained through X-ray crystallography, biochemical assays, and numerical simulation to construct a model of the enzyme catalytic pathway. The NDM-1 enzyme interacts with the substrate solely through zinc, or other metals, bound in the active site, explaining the observed lack of specificity against a broad range of beta-lactam antibiotic agents. The zinc ions also serve to activate a water molecule that hydrolyzes the beta-lactam ring through a proton shuttle.

-	~~Approved Drugs Containing Thiols as Inhibitors of Metallo~~-~~beta-lactamases~~: ~~Strategy To Combat Multidrug-Resistant Bacteria~~.,~~Klingler FM~~, ~~Wichelhaus TA~~, ~~Frank D, Cuesta-Bernal~~ J, ~~El-Delik~~ J, ~~Muller HF, Sjuts H, Gottig S, Koenigs~~ A~~, Pos KM, Pogoryelov D, Proschak E~~ J ~~Med Chem~~. ~~2015 Apr 23~~;58(8):~~3626~~-30. doi: 10.~~1021~~/~~jm501844d~~. Epub ~~2015 Apr 13~~. PMID:~~25815530~~<ref>PMID:~~25815530~~</ref>	+	NDM-1, the ultimate promiscuous enzyme: substrate recognition and catalytic mechanism.,Kim Y, Cunningham MA, Mire J, Tesar C, Sacchettini J, Joachimiak A FASEB J. 2013 May;27(5):1917-27. doi: 10.1096/fj.12-224014. Epub 2013 Jan 30. PMID:23363572<ref>PMID:23363572</ref>

	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 6ex7" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6ex7" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta-lactamase\|Beta-lactamase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:06, 13 December 2017

OCA — Wed, 13 Dec 2017 07:06:31 GMT

←Older revision		Revision as of 07:06, 13 December 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6ex7 is ~~ON HOLD~~	+	==Crystal structure of NDM-1 metallo-beta-lactamase in complex with Cd ions and a hydrolyzed beta-lactam ligand - new refinement==
		+	<StructureSection load='6ex7' size='340' side='right' caption='[[6ex7]], [[Resolution\|resolution]] 1.95Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6ex7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EX7 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=TOE:2-[2-(2-METHOXY-ETHOXY)-ETHOXY]-ETHOXYL'>TOE</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hky\|4hky]]</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=6ex7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ex7 OCA], [http://pdbe.org/6ex7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ex7 RCSB], [http://www.ebi.ac.uk/pdbsum/6ex7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ex7 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/BLAN1_KLEPN BLAN1_KLEPN]] Confers resistance to many beta-lactam antibiotics, including some carbapenems. Does not confer resistance to the polymixin colistin or the fluoroquinolone ciprofloxacin.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Resistance to beta-lactam antibiotics can be mediated by metallo-beta-lactamase enzymes (MBLs). An MBL inhibitor could restore the effectiveness of beta-lactams. We report on the evaluation of approved thiol-containing drugs as inhibitors of NDM-1, VIM-1, and IMP-7. Drugs were assessed by a novel assay using a purchasable fluorescent substrate and thermal shift. Best compounds were tested in antimicrobial susceptibility assay. Using these orthogonal screening methods, we identified drugs that restored the activity of imipenem.

-	~~Authors~~: ~~Kim, Y~~., ~~Raczynska~~, ~~J.E.~~, ~~Shabalin~~, ~~I.G.~~, ~~Jaskolski~~, M., ~~Minor~~, ~~W., Wlodawer~~, A., ~~Tesar~~, ~~C., Jedrzejczak, R., Babnigg~~, J.~~, Mire, J~~.~~, Sacchettini, J~~.~~, Joachimiak, A~~.	+	Approved Drugs Containing Thiols as Inhibitors of Metallo-beta-lactamases: Strategy To Combat Multidrug-Resistant Bacteria.,Klingler FM, Wichelhaus TA, Frank D, Cuesta-Bernal J, El-Delik J, Muller HF, Sjuts H, Gottig S, Koenigs A, Pos KM, Pogoryelov D, Proschak E J Med Chem. 2015 Apr 23;58(8):3626-30. doi: 10.1021/jm501844d. Epub 2015 Apr 13. PMID:25815530<ref>PMID:25815530</ref>

-	~~Description: Crystal structure~~ of ~~NDM~~-~~1 metallo~~-~~beta-lactamase in complex with Cd ions and a hydrolyzed beta-lactam ligand -new refinement~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Tesar, C~~]]	+	<div class="pdbe-citations 6ex7" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Mire~~, J]]	+	== References ==
-	[[Category: ~~Wlodawer~~, A]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Beta-lactamase]]
		+	[[Category: Babnigg, J]]
		+	[[Category: Jaskolski, M]]
	[[Category: Jedrzejczak, R]]		[[Category: Jedrzejczak, R]]
-	[[Category: ~~Shabalin~~, ~~I.G~~]]	+	[[Category: Joachimiak, A]]
	[[Category: Kim, Y]]		[[Category: Kim, Y]]
-	[[Category: Babnigg, J]]
	[[Category: Minor, W]]		[[Category: Minor, W]]
-	[[Category: ~~Joachimiak~~, A]]	+	[[Category: Mire, J]]
		+	[[Category: Raczynska, J E]]
	[[Category: Sacchettini, J]]		[[Category: Sacchettini, J]]
-	[[Category: ~~Jaskolski~~, M]]	+	[[Category: Shabalin, I G]]
-	[[Category: ~~Raczynska~~, ~~J.E~~]]	+	[[Category: Tesar, C]]
		+	[[Category: Wlodawer, A]]
		+	[[Category: Hydrolase]]
		+	[[Category: Metallo-beta-lactamase]]
		+	[[Category: Ndm-1]]

OCA: Protected "6ex7" [edit=sysop:move=sysop]

OCA — Wed, 15 Nov 2017 06:31:11 GMT

Protected "6ex7" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:31, 15 November 2017

OCA: New page: '''Unreleased structure''' The entry 6ex7 is ON HOLD Authors: Kim, Y., Raczynska, J.E., Shabalin, I.G., Jaskolski, M., Minor, W., Wlodawer, A., Tesar, C., Jedrzejczak, R., Babnigg, J., ...

OCA — Wed, 15 Nov 2017 06:31:10 GMT

New page: '''Unreleased structure''' The entry 6ex7 is ON HOLD Authors: Kim, Y., Raczynska, J.E., Shabalin, I.G., Jaskolski, M., Minor, W., Wlodawer, A., Tesar, C., Jedrzejczak, R., Babnigg, J., ...

New page

'''Unreleased structure'''

The entry 6ex7 is ON HOLD

Authors: Kim, Y., Raczynska, J.E., Shabalin, I.G., Jaskolski, M., Minor, W., Wlodawer, A., Tesar, C., Jedrzejczak, R., Babnigg, J., Mire, J., Sacchettini, J., Joachimiak, A.

Description: Crystal structure of NDM-1 metallo-beta-lactamase in complex with Cd ions and a hydrolyzed beta-lactam ligand -new refinement
[[Category: Unreleased Structures]]
[[Category: Tesar, C]]
[[Category: Mire, J]]
[[Category: Wlodawer, A]]
[[Category: Jedrzejczak, R]]
[[Category: Shabalin, I.G]]
[[Category: Kim, Y]]
[[Category: Babnigg, J]]
[[Category: Minor, W]]
[[Category: Joachimiak, A]]
[[Category: Sacchettini, J]]
[[Category: Jaskolski, M]]
[[Category: Raczynska, J.E]]