6mey - Revision history

OCA at 06:30, 11 October 2023

2023-10-11T06:30:12Z

←Older revision		Revision as of 06:30, 11 October 2023
Line 3:		Line 3:
	<StructureSection load='6mey' size='340' side='right'caption='[[6mey]], [[Resolution\|resolution]] 1.42Å' scene=''>		<StructureSection load='6mey' size='340' side='right'caption='[[6mey]], [[Resolution\|resolution]] 1.42Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6mey]] 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=6MEY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6MEY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6mey]] 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=6MEY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MEY FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name~~=~~'pdbligand=ACT:ACETATE+ION'>ACT</scene~~>, ~~<scene name='pdbligand=O5E:(2R)-2-phenyl-2-(phenylamino)-N-(1H-tetrazol-5-yl)acetamide'>O5E</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]] 1.42Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>bla, kpc, kpc1 ([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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=O5E:(2R)-2-phenyl-2-(phenylamino)-N-(1H-tetrazol-5-yl)acetamide'>O5E</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=6mey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mey OCA], [https://pdbe.org/6mey PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mey RCSB], [https://www.ebi.ac.uk/pdbsum/6mey PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mey 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=6mey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mey OCA], [~~http~~://pdbe.org/6mey PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6mey RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6mey PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6mey ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/BLKPC_KLEPN BLKPC_KLEPN]] Hydrolyzes carbapenems, penicillins, cephalosporins and monobactams with varying efficiency.	+	[https://www.uniprot.org/uniprot/BLKPC_KLEPN BLKPC_KLEPN] Hydrolyzes carbapenems, penicillins, cephalosporins and monobactams with varying efficiency.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6mey" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6mey" 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: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Tetrazole~~]]	+

OCA at 07:30, 26 June 2019

2019-06-26T07:30:01Z

←Older revision		Revision as of 07:30, 26 June 2019
Line 3:		Line 3:
	<StructureSection load='6mey' size='340' side='right'caption='[[6mey]], [[Resolution\|resolution]] 1.42Å' scene=''>		<StructureSection load='6mey' size='340' side='right'caption='[[6mey]], [[Resolution\|resolution]] 1.42Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6mey]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MEY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MEY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6mey]] 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=6MEY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MEY FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=O5E:(2R)-2-phenyl-2-(phenylamino)-N-(1H-tetrazol-5-yl)acetamide'>O5E</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=O5E:(2R)-2-phenyl-2-(phenylamino)-N-(1H-tetrazol-5-yl)acetamide'>O5E</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">bla, kpc, kpc1 ([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=6mey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mey OCA], [http://pdbe.org/6mey PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mey RCSB], [http://www.ebi.ac.uk/pdbsum/6mey PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mey 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=6mey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mey OCA], [http://pdbe.org/6mey PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mey RCSB], [http://www.ebi.ac.uk/pdbsum/6mey PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mey ProSAT]</span></td></tr>

OCA at 06:01, 17 April 2019

2019-04-17T06:01:49Z

←Older revision		Revision as of 06:01, 17 April 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6mey is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of KPC-2 with compound 9==
		+	<StructureSection load='6mey' size='340' side='right'caption='[[6mey]], [[Resolution\|resolution]] 1.42Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6mey]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MEY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MEY FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=O5E:(2R)-2-phenyl-2-(phenylamino)-N-(1H-tetrazol-5-yl)acetamide'>O5E</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6mey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mey OCA], [http://pdbe.org/6mey PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mey RCSB], [http://www.ebi.ac.uk/pdbsum/6mey PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mey ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/BLKPC_KLEPN BLKPC_KLEPN]] Hydrolyzes carbapenems, penicillins, cephalosporins and monobactams with varying efficiency.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Serine and metallo-carbapenemases are a serious health concern due to their capability to hydrolyze nearly all beta-lactam antibiotics. However, the molecular basis for their unique broad-spectrum substrate profile is poorly understood, particularly for serine carbapenemases, such as KPC-2. Using substrates and newly identified small molecules, we compared the ligand binding properties of KPC-2 with the noncarbapenemase CTX-M-14, both of which are Class A beta-lactamases with highly similar active sites. Notably, compared to CTX-M-14, KPC-2 was more potently inhibited by hydrolyzed beta-lactam products (product inhibition), as well as by a series of novel tetrazole-based inhibitors selected from molecular docking against CTX-M-14. Together with complex crystal structures, these data suggest that the KPC-2 active site has an enhanced ability to form favorable interactions with substrates and small molecule ligands due to its increased hydrophobicity and flexibility. Such properties are even more pronounced in metallo-carbapenemases, such as NDM-1, which was also inhibited by some of the novel tetrazole compounds, including one displaying comparable low muM affinities against both KPC-2 and NDM-1. Our results suggest that carbapenemase activity confers an evolutionary advantage on producers via a broad beta-lactam substrate scope but also a mechanistic Achilles' heel that can be exploited for new inhibitor discovery. The complex structures demonstrate, for the first time, how noncovalent inhibitors can be engineered to simultaneously target both serine and metallo-carbapenemases. Despite the relatively modest activity of the current compounds, these studies also demonstrate that hydrolyzed products and tetrazole-based chemotypes can provide valuable starting points for broad-spectrum inhibitor discovery against carbapenemases.

-	~~Authors: Akhtar~~, A., ~~Chen~~, Y.	+	Active-Site Druggability of Carbapenemases and Broad-Spectrum Inhibitor Discovery.,Torelli NJ, Akhtar A, DeFrees K, Jaishankar P, Pemberton OA, Zhang X, Johnson C, Renslo AR, Chen Y ACS Infect Dis. 2019 Apr 15. doi: 10.1021/acsinfecdis.9b00052. PMID:30942078<ref>PMID:30942078</ref>

-	~~Description: Crystal structure~~ of ~~KPC~~-~~2 with compound 9~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6mey" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Beta-lactamase]]
		+	[[Category: Large Structures]]
	[[Category: Akhtar, A]]		[[Category: Akhtar, A]]
	[[Category: Chen, Y]]		[[Category: Chen, Y]]
		+	[[Category: Carbapenemase]]
		+	[[Category: Complex]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Inhibitor]]
		+	[[Category: Tetrazole]]

OCA at 06:23, 30 January 2019

2019-01-30T06:23:31Z

←Older revision		Revision as of 06:23, 30 January 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6mey is ON HOLD	+	The entry 6mey is ON HOLD until Paper Publication

	Authors: Akhtar, A., Chen, Y.		Authors: Akhtar, A., Chen, Y.

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

2018-09-19T18:25:20Z

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

←Older revision

Revision as of 18:25, 19 September 2018

OCA: New page: '''Unreleased structure''' The entry 6mey is ON HOLD Authors: Akhtar, A., Chen, Y. Description: Crystal structure of KPC-2 with compound 9 Category: Unreleased Structures [[Categor...

2018-09-19T18:25:18Z

New page: '''Unreleased structure''' The entry 6mey is ON HOLD Authors: Akhtar, A., Chen, Y. Description: Crystal structure of KPC-2 with compound 9 Category: Unreleased Structures [[Categor...

New page

'''Unreleased structure'''

The entry 6mey is ON HOLD

Authors: Akhtar, A., Chen, Y.

Description: Crystal structure of KPC-2 with compound 9
[[Category: Unreleased Structures]]
[[Category: Akhtar, A]]
[[Category: Chen, Y]]