6ny7 - Revision history

OCA at 07:01, 11 October 2023

OCA — Wed, 11 Oct 2023 07:01:35 GMT

←Older revision		Revision as of 07:01, 11 October 2023
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	<StructureSection load='6ny7' size='340' side='right'caption='[[6ny7]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='6ny7' size='340' side='right'caption='[[6ny7]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ny7]] is a 1 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=6NY7 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6NY7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ny7]] is a 1 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=6NY7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NY7 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=L8J:~~[~~(5,7-dibromo-2-oxo-~~1~~,2-dihydroquinolin-~~4~~-yl)methyl]phosphonic+acid'>L8J</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.4Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~blaNDM-1~~, ~~bla NDM~~-~~1, blaNDM~~-~~1_1, blaNDM~~-~~1_2, blaNDM-1_3, blaNDM1, NDM~~-1, ~~C3483_29595, C7V41_28630, D647_p47098, DDJ63_29735, DZB15_28435, EC13450_007, NCTC13443_00040, p2146_00143, pCRE380_21, PMK1_ndm00067, PMK1_ndm00076, PMK1_ndm00085, pN11x00042NDM_090, pNDM~~-SX04_5, pNDM10469_138, SAMEA3531848_05178, SAMEA4394746_03823, TR3_031, TR4_031 ([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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L8J:[(5,7-dibromo-2-oxo-1,2-dihydroquinolin-4-yl)methyl]phosphonic+acid'>L8J</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<~~tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks~~'>~~[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6]~~ </~~span~~></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ny7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ny7 OCA], [https://pdbe.org/6ny7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ny7 RCSB], [https://www.ebi.ac.uk/pdbsum/6ny7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ny7 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=6ny7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ny7 OCA], [~~http~~://pdbe.org/6ny7 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6ny7 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6ny7 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6ny7 ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[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 ==
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	</div>		</div>
	<div class="pdbe-citations 6ny7" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6ny7" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta-lactamase 3D structures\|Beta-lactamase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Beta-lactamase~~]]	+	[[Category: Klebsiella pneumoniae]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Akhtar, A]]	+	[[Category: Akhtar A]]
-	[[Category: Chen, Y]]	+	[[Category: Chen Y]]
-	~~[[Category: Carbapenemase]]~~	+
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Phosphonate~~]]	+

OCA at 06:13, 10 October 2019

OCA — Thu, 10 Oct 2019 06:13:03 GMT

←Older revision		Revision as of 06:13, 10 October 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6ny7 is ~~ON HOLD~~	+	==Crystal Structure of NDM-1 D199N with Compound 16==
		+	<StructureSection load='6ny7' size='340' side='right'caption='[[6ny7]], [[Resolution\|resolution]] 1.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6ny7]] is a 1 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=6NY7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NY7 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L8J:[(5,7-dibromo-2-oxo-1,2-dihydroquinolin-4-yl)methyl]phosphonic+acid'>L8J</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">blaNDM-1, bla NDM-1, blaNDM-1_1, blaNDM-1_2, blaNDM-1_3, blaNDM1, NDM-1, C3483_29595, C7V41_28630, D647_p47098, DDJ63_29735, DZB15_28435, EC13450_007, NCTC13443_00040, p2146_00143, pCRE380_21, PMK1_ndm00067, PMK1_ndm00076, PMK1_ndm00085, pN11x00042NDM_090, pNDM-SX04_5, pNDM10469_138, SAMEA3531848_05178, SAMEA4394746_03823, TR3_031, TR4_031 ([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='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=6ny7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ny7 OCA], [http://pdbe.org/6ny7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ny7 RCSB], [http://www.ebi.ac.uk/pdbsum/6ny7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ny7 ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Gram-negative pathogens expressing serine beta-lactamases (SBLs) and metallo-beta-lactamases (MBLs), especially those with carbapenemase activity, threaten the clinical utility of almost all beta-lactam antibiotics. Here we describe the discovery of a heteroaryl phosphonate scaffold that exhibits noncovalent cross-class inhibition of representative carbapenemases, specifically the SBL KPC-2 and the MBLs NDM-1 and VIM-2. The most potent lead, compound 16, exhibited low nM to low muM inhibition of KPC-2, NDM-1, and VIM-2. Compound 16 potentiated imipenem efficacy against resistant clinical and laboratory bacterial strains expressing carbapenemases while showing some cytotoxicity toward human HEK293T cells only at concentrations above 100 mug/mL. Complex structures with KPC-2, NDM-1, and VIM-2 demonstrate how these inhibitors achieve high binding affinity to both enzyme classes. These findings provide a structurally and mechanistically new scaffold for drug discovery targeting multidrug resistant Gram-negative pathogens and more generally highlight the active site features of carbapenemases that can be leveraged for lead discovery.

-	~~Authors~~:	+	Heteroaryl Phosphonates as Noncovalent Inhibitors of Both Serine- and Metallocarbapenemases.,Pemberton OA, Jaishankar P, Akhtar A, Adams JL, Shaw LN, Renslo AR, Chen Y J Med Chem. 2019 Sep 26;62(18):8480-8496. doi: 10.1021/acs.jmedchem.9b00728. Epub, 2019 Sep 13. PMID:31483651<ref>PMID:31483651</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6ny7" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Beta-lactamase]]
		+	[[Category: Large Structures]]
		+	[[Category: Akhtar, A]]
		+	[[Category: Chen, Y]]
		+	[[Category: Carbapenemase]]
		+	[[Category: Complex]]
		+	[[Category: Hydrolase]]
		+	[[Category: Inhibitor]]
		+	[[Category: Phosphonate]]

OCA: Protected "6ny7" [edit=sysop:move=sysop]

OCA — Thu, 21 Feb 2019 05:13:10 GMT

Protected "6ny7" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:13, 21 February 2019

OCA: New page: '''Unreleased structure''' The entry 6ny7 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Thu, 21 Feb 2019 05:13:09 GMT

New page: '''Unreleased structure''' The entry 6ny7 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6ny7 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]