OCA at 08:05, 6 December 2023

OCA — Wed, 06 Dec 2023 08:05:48 GMT

←Older revision		Revision as of 08:05, 6 December 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8tn0 is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of KPC-44 carbapenemase w/o cryoprotectant==
		+	<StructureSection load='8tn0' size='340' side='right'caption='[[8tn0]], [[Resolution\|resolution]] 1.31Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8tn0]] 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=8TN0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8TN0 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]] 1.31Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=8tn0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8tn0 OCA], [https://pdbe.org/8tn0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8tn0 RCSB], [https://www.ebi.ac.uk/pdbsum/8tn0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8tn0 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/A0A4Y5JTU1_KLEPN A0A4Y5JTU1_KLEPN]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Klebsiella pneumoniae carbapenemase 2 (KPC-2) is an important source of drug resistance as it can hydrolyze and inactivate virtually all beta-lactam antibiotics. KPC-2 is potently inhibited by avibactam via formation of a reversible carbamyl linkage of the inhibitor with the catalytic serine of the enzyme. However, the use of avibactam in combination with ceftazidime (CAZ-AVI) has led to the emergence of CAZ-AVI resistant variants of KPC-2 in clinical settings. One such variant, KPC-44, bears a 15 amino-acid duplication in one of the active site loops (270-loop). Here, we show that the KPC-44 variant exhibits higher catalytic efficiency in hydrolyzing ceftazidime, lower efficiency towards imipenem and meropenem, and a similar efficiency in hydrolyzing ampicillin, when compared to the wild-type KPC-2 enzyme. In addition, the KPC-44 variant enzyme exhibits 12-fold lower avibactam carbamylation efficiency than the KPC-2 enzyme. An X-ray crystal structure of KPC-44 showed that the 15 amino acid duplication results in an extended and partially disordered 270-loop and also changes the conformation of the adjacent 240-loop, which in turn has altered interactions with the active-site omega loop. Furthermore, a structure of KPC-44 with avibactam revealed that formation of the covalent complex results in further disorder in the 270-loop, suggesting that rearrangement of the 270-loop of KPC-44 facilitates avibactam carbamylation. These results suggest that the duplication of 15 amino acids in the KPC-44 enzyme leads to resistance to CAZ-AVI by modulating the stability and conformation of the 270-, 240-, and omega-loops.

-	~~Authors:~~ Sun, Z., ~~Palzkill, T.~~, Hu, L., ~~Lin, H.~~, Sankaran, B., Wang, J., Prasad, B.	+	Klebsiella pneumoniae carbapenemase variant 44 (KPC-44) acquires ceftazidime-avibactam resistance by altering the conformation of active site loops.,Sun Z, Lin H, Hu L, Neetu N, Sankaran B, Wang J, Prasad BVV, Palzkill T J Biol Chem. 2023 Nov 22:105493. doi: 10.1016/j.jbc.2023.105493. PMID:38000656<ref>PMID:38000656</ref>

-	~~Description: Crystal structure~~ of ~~KPC~~-~~44 carbapenemase w~~/~~o cryoprotectant~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Hu, L]]	+	<div class="pdbe-citations 8tn0" style="background-color:#fffaf0;"></div>
-	[[Category: Lin, H]]	+	== References ==
-	[[Category: ~~Prasad, B~~]]	+	<references/>
-	[[Category: ~~Palzkill, T~~]]	+	__TOC__
-	[[Category: Sankaran, B]]	+	</StructureSection>
-	[[Category: Sun, Z]]	+	[[Category: Klebsiella pneumoniae]]
-	[[Category: Wang, J]]	+	[[Category: Large Structures]]
		+	[[Category: Hu L]]
		+	[[Category: Lin H]]
		+	[[Category: Palzkill T]]
		+	[[Category: Prasad B]]
		+	[[Category: Sankaran B]]
		+	[[Category: Sun Z]]
		+	[[Category: Wang J]]

OCA at 06:55, 16 August 2023

OCA — Wed, 16 Aug 2023 06:55:18 GMT

←Older revision		Revision as of 06:55, 16 August 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8tn0 is ON HOLD	+	The entry 8tn0 is ON HOLD until Paper Publication

	Authors: Sun, Z., Palzkill, T., Hu, L., Lin, H., Sankaran, B., Wang, J., Prasad, B.		Authors: Sun, Z., Palzkill, T., Hu, L., Lin, H., Sankaran, B., Wang, J., Prasad, B.
Line 9:		Line 9:
	[[Category: Hu, L]]		[[Category: Hu, L]]
	[[Category: Lin, H]]		[[Category: Lin, H]]
		+	[[Category: Prasad, B]]
		+	[[Category: Palzkill, T]]
	[[Category: Sankaran, B]]		[[Category: Sankaran, B]]
	[[Category: Sun, Z]]		[[Category: Sun, Z]]
	[[Category: Wang, J]]		[[Category: Wang, J]]
-	[[Category: Prasad, B]]
-	[[Category: Palzkill, T]]

OCA: Protected "8tn0" [edit=sysop:move=sysop]

OCA — Wed, 09 Aug 2023 04:17:26 GMT

Protected "8tn0" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:17, 9 August 2023

OCA: New page: '''Unreleased structure''' The entry 8tn0 is ON HOLD Authors: Sun, Z., Palzkill, T., Hu, L., Lin, H., Sankaran, B., Wang, J., Prasad, B. Description: Crystal structure of KPC-44 carbap...

OCA — Wed, 09 Aug 2023 04:17:25 GMT

New page: '''Unreleased structure''' The entry 8tn0 is ON HOLD Authors: Sun, Z., Palzkill, T., Hu, L., Lin, H., Sankaran, B., Wang, J., Prasad, B. Description: Crystal structure of KPC-44 carbap...

New page

'''Unreleased structure'''

The entry 8tn0 is ON HOLD

Authors: Sun, Z., Palzkill, T., Hu, L., Lin, H., Sankaran, B., Wang, J., Prasad, B.

Description: Crystal structure of KPC-44 carbapenemase w/o cryoprotectant
[[Category: Unreleased Structures]]
[[Category: Hu, L]]
[[Category: Lin, H]]
[[Category: Sankaran, B]]
[[Category: Sun, Z]]
[[Category: Wang, J]]
[[Category: Prasad, B]]
[[Category: Palzkill, T]]

8tn0 - Revision history

OCA at 08:05, 6 December 2023

OCA at 06:55, 16 August 2023

OCA: Protected "8tn0" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8tn0 is ON HOLD Authors: Sun, Z., Palzkill, T., Hu, L., Lin, H., Sankaran, B., Wang, J., Prasad, B. Description: Crystal structure of KPC-44 carbap...