OCA at 05:56, 23 August 2023

2023-08-23T05:56:20Z

←Older revision		Revision as of 05:56, 23 August 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8sko is ~~ON HOLD until Paper~~ Publication	+	==X-ray structure of the NDM-4 beta-lactamase from Klebsiella pneumonia with L-Captopril bound==
		+	<StructureSection load='8sko' size='340' side='right'caption='[[8sko]], [[Resolution\|resolution]] 1.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8sko]] 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=8SKO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SKO FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.3Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=X8Z:L-CAPTOPRIL'>X8Z</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8sko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8sko OCA], [https://pdbe.org/8sko PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8sko RCSB], [https://www.ebi.ac.uk/pdbsum/8sko PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8sko ProSAT]</span></td></tr>
		+	</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;">
		+	== Publication Abstract from PubMed ==
		+	The bacterial metallo-beta-lactamases (MBLs) catalyze the inactivation of beta-lactam antibiotics. Identifying novel pharmacophores remains crucial for the clinical development of additional MBL inhibitors. Previously, 1-hydroxypyridine-2(1H)-thione-6-carboxylic acid, hereafter referred to as 1,2-HPT-6-COOH, was reported as a low cytotoxic nanomolar beta-lactamase inhibitor of Verona-integron-encoded metallo-beta-lactamase 2 (VIM-2), capable of rescuing beta-lactam antibiotic activity. In this study, we explore its exact mechanism of inhibition and the extent of its activity through structural characterization of its binding to New Delhi metallo-beta-lactamase 4 (NDM-4) and its inhibitory activity against both NDM-1 and NDM-4. Of all the structure-validated MBL inhibitors available, 1,2-HPT-6-COOH is the first discovered compound capable of forming an octahedral coordination sphere with Zn2 of the binuclear metal center. This unexpected mechanism of action provides important insight for the further optimization of 1,2-HPT-6-COOH and the identification of additional pharmacophores for MBL inhibition.

-	~~Authors~~: Thoden, J.B.~~, Holden, H~~.M.	+	Characterization of a novel inhibitor for the New Delhi metallo-beta-lactamase-4: implications for drug design and combating bacterial drug resistance.,Thoden JB, Benin BM, Priebe A, Shin WS, Muthyala R, Sham YY, Holden HM J Biol Chem. 2023 Aug 5:105135. doi: 10.1016/j.jbc.2023.105135. PMID:37549809<ref>PMID:37549809</ref>

-	~~Description: X-ray structure~~ of the ~~NDM~~-~~4 beta~~-~~lactamase from~~ Klebsiella ~~pneumonia with L-Captopril bound~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Thoden, J.B~~]]	+	<div class="pdbe-citations 8sko" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Holden, H.M~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Klebsiella pneumoniae]]
		+	[[Category: Large Structures]]
		+	[[Category: Holden HM]]
		+	[[Category: Thoden JB]]

OCA at 05:53, 18 May 2023

2023-05-18T05:53:08Z

←Older revision		Revision as of 05:53, 18 May 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8sko is ON HOLD	+	The entry 8sko is ON HOLD until Paper Publication

	Authors: Thoden, J.B., Holden, H.M.		Authors: Thoden, J.B., Holden, H.M.

OCA: Protected "8sko" [edit=sysop:move=sysop]

2023-04-26T15:29:29Z

Protected "8sko" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:29, 26 April 2023

OCA: New page: '''Unreleased structure''' The entry 8sko is ON HOLD Authors: Thoden, J.B., Holden, H.M. Description: X-ray structure of the NDM-4 beta-lactamase from Klebsiella pneumonia with L-Capto...

2023-04-26T15:29:27Z

New page: '''Unreleased structure''' The entry 8sko is ON HOLD Authors: Thoden, J.B., Holden, H.M. Description: X-ray structure of the NDM-4 beta-lactamase from Klebsiella pneumonia with L-Capto...

New page

'''Unreleased structure'''

The entry 8sko is ON HOLD

Authors: Thoden, J.B., Holden, H.M.

Description: X-ray structure of the NDM-4 beta-lactamase from Klebsiella pneumonia with L-Captopril bound
[[Category: Unreleased Structures]]
[[Category: Thoden, J.B]]
[[Category: Holden, H.M]]

8sko - Revision history

OCA at 05:56, 23 August 2023

OCA at 05:53, 18 May 2023

OCA: Protected "8sko" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8sko is ON HOLD Authors: Thoden, J.B., Holden, H.M. Description: X-ray structure of the NDM-4 beta-lactamase from Klebsiella pneumonia with L-Capto...