6z22 - Revision history

OCA at 13:40, 24 January 2024

OCA — Wed, 24 Jan 2024 13:40:17 GMT

←Older revision		Revision as of 13:40, 24 January 2024
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	<StructureSection load='6z22' size='340' side='right'caption='[[6z22]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='6z22' size='340' side='right'caption='[[6z22]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6z22]] is a 1 chain structure with sequence from [https://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=6Z22 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z22 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6z22]] 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=6Z22 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z22 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>~~, ~~<scene name='pdbligand=SO4:SULFATE+ION'>SO4</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"~~>blaKPC-4, blaKPC-2 ([https://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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>~~[https://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [https://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=6z22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z22 OCA], [https://pdbe.org/6z22 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z22 RCSB], [https://www.ebi.ac.uk/pdbsum/6z22 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z22 ProSAT]</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=6z22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z22 OCA], [https://pdbe.org/6z22 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z22 RCSB], [https://www.ebi.ac.uk/pdbsum/6z22 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z22 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[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 ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Beta-lactamase~~]]	+	[[Category: Klebsiella pneumoniae]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Hinchliffe, P]]	+	[[Category: Hinchliffe P]]
-	[[Category: Spencer, J]]	+	[[Category: Spencer J]]
-	[[Category: Tooke~~, C L]]~~	+	[[Category: Tooke CL]]
-	~~[[Category: 3-layer alpha-beta-alpha sandwich]]~~	+
-	~~[[Category: Antimicrobial protein]]~~	+
-	~~[[Category: Part of the dd-peptidase and beta-lactamase superfamily]]~~	+
-	~~[[Category: Unliganded beta-lactamase~~]]	+

OCA at 09:09, 21 July 2021

OCA — Wed, 21 Jul 2021 09:09:10 GMT

←Older revision		Revision as of 09:09, 21 July 2021
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	==Crystal structure of deacylation mutant KPC-4 (E166Q)==		==Crystal structure of deacylation mutant KPC-4 (E166Q)==
-	<StructureSection load='6z22' size='340' side='right'caption='[[6z22]]' scene=''>	+	<StructureSection load='6z22' size='340' side='right'caption='[[6z22]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Z22 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6Z22 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6z22]] is a 1 chain structure with sequence from [https://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=6Z22 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z22 FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6z22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z22 OCA], [~~http~~://pdbe.org/6z22 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6z22 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6z22 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6z22 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">blaKPC-4, blaKPC-2 ([https://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'>[https://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [https://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=6z22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z22 OCA], [https://pdbe.org/6z22 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z22 RCSB], [https://www.ebi.ac.uk/pdbsum/6z22 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z22 ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Class A serine beta-lactamases (SBLs) are key antibiotic resistance determinants in Gram-negative bacteria. SBLs neutralize beta-lactams via a hydrolytically labile covalent acyl-enzyme intermediate. Klebsiella pneumoniae carbapenemase (KPC) is a widespread SBL that hydrolyzes carbapenems, the most potent beta-lactams; known KPC variants differ in turnover of expanded-spectrum oxyimino-cephalosporins (ESOCs), e.g. cefotaxime and ceftazidime. Here, we compare ESOC hydrolysis by the parent enzyme KPC-2 and its clinically observed double variant (P104R/V240G) KPC-4. Kinetic analyses show KPC-2 hydrolyzes cefotaxime more efficiently than the bulkier ceftazidime, with improved ESOC turnover by KPC-4 resulting from enhanced turnover (kcat), rather than binding (KM). High-resolution crystal structures of ESOC acyl-enzyme complexes with deacylation-deficient (E166Q) KPC-2 and KPC-4 mutants show that ceftazidime acylation causes rearrangement of three loops; the Omega-, 240- and 270-loops, that border the active site. However, these rearrangements are less pronounced in the KPC-4 than the KPC-2 ceftazidime acyl-enzyme, and are not observed in the KPC-2:cefotaxime acyl-enzyme. Molecular dynamics simulations of KPC:ceftazidime acyl-enyzmes reveal that the deacylation general base E166, located on the Omega-loop, adopts two distinct conformations in KPC-2, either pointing 'in' or 'out' of the active site; with only the 'in' form compatible with deacylation. The 'out' conformation was not sampled in the KPC-4 acyl-enzyme, indicating that efficient ESOC breakdown is dependent upon the ordering and conformation of the KPC Omega-loop. The results explain how point mutations expand the activity spectrum of the clinically important KPC SBLs to include ESOCs through their effects on the conformational dynamics of the acyl-enzyme intermediate.
		+
		+	Natural variants modify Klebsiella pneumoniae carbapenemase (KPC) acyl-enzyme conformational dynamics to extend antibiotic resistance.,Tooke CL, Hinchliffe P, Bonomo RA, Schofield CJ, Mulholland AJ, Spencer J J Biol Chem. 2020 Nov 30. pii: RA120.016461. doi: 10.1074/jbc.RA120.016461. PMID:33257320<ref>PMID:33257320</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6z22" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta-lactamase 3D structures\|Beta-lactamase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Beta-lactamase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Hinchliffe P]]	+	[[Category: Hinchliffe, P]]
-	[[Category: Spencer J]]	+	[[Category: Spencer, J]]
-	[[Category: Tooke CL]]	+	[[Category: Tooke, C L]]
		+	[[Category: 3-layer alpha-beta-alpha sandwich]]
		+	[[Category: Antimicrobial protein]]
		+	[[Category: Part of the dd-peptidase and beta-lactamase superfamily]]
		+	[[Category: Unliganded beta-lactamase]]

OCA at 10:34, 24 December 2020

OCA — Thu, 24 Dec 2020 10:34:13 GMT

←Older revision		Revision as of 10:34, 24 December 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6z22 is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of deacylation mutant KPC-4 (E166Q)==
-		+	<StructureSection load='6z22' size='340' side='right'caption='[[6z22]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Z22 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6Z22 FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6z22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z22 OCA], [http://pdbe.org/6z22 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6z22 RCSB], [http://www.ebi.ac.uk/pdbsum/6z22 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6z22 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Hinchliffe P]]
		+	[[Category: Spencer J]]
		+	[[Category: Tooke CL]]

OCA at 05:18, 3 June 2020

OCA — Wed, 03 Jun 2020 05:18:15 GMT

←Older revision		Revision as of 05:18, 3 June 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6z22 is ON HOLD	+	The entry 6z22 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6z22" [edit=sysop:move=sysop]

OCA — Wed, 20 May 2020 04:34:42 GMT

Protected "6z22" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:34, 20 May 2020

OCA: New page: '''Unreleased structure''' The entry 6z22 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 20 May 2020 04:34:41 GMT

New page: '''Unreleased structure''' The entry 6z22 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6z22 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]