7ass - Revision history

OCA at 12:15, 1 February 2024

OCA — Thu, 01 Feb 2024 12:15:27 GMT

←Older revision		Revision as of 12:15, 1 February 2024
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	<StructureSection load='7ass' size='340' side='right'caption='[[7ass]], [[Resolution\|resolution]] 1.91Å' scene=''>		<StructureSection load='7ass' size='340' side='right'caption='[[7ass]], [[Resolution\|resolution]] 1.91Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7ass]] is a 4 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=7ASS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ASS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7ass]] is a 4 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=7ASS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ASS FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>~~, ~~<scene name='pdbligand=RYE:hydrolyzed+ceftazidime'>RYE</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]] 1.91Å</td></tr>
-	<tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=~~KCX~~:~~LYSINE~~+~~NZ-CARBOXYLIC+ACID~~'>~~KCX~~</scene><~~/td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=RYE:hydrolyzed+ceftazidime'>RYE</scene></td></tr>
-	~~<tr id~~='~~gene'><td class~~=~~"sblockLbl"><b>[[Gene\|Gene~~:~~]]</b~~></td>~~<td class="sblockDat">bla OXA-48~~, bla_2, bla_3, blaOXA-48, B6R99_29845, G5637_27540, GJJ01_28680, KPE71T_00045, SAMEA3649466_05396, SAMEA3673128_05462, SAMEA3729780_05587 ([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=7ass FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ass OCA], [https://pdbe.org/7ass PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ass RCSB], [https://www.ebi.ac.uk/pdbsum/7ass PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ass 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=7ass FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ass OCA], [https://pdbe.org/7ass PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ass RCSB], [https://www.ebi.ac.uk/pdbsum/7ass PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ass ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q6XEC0_KLEPN Q6XEC0_KLEPN]
	<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: Frohlich, C]]	+	[[Category: Frohlich C]]
-	[[Category: Leiros, H ~~K.S]]~~	+	[[Category: Leiros H-KS]]
-	~~[[Category: Antibiotic]]~~	+
-	~~[[Category: Carbapenem]]~~	+
-	~~[[Category: Carbapenemase]]~~	+
-	~~[[Category: Ceftazidime]]~~	+
-	~~[[Category: Collateral sensitivity]]~~	+
-	~~[[Category: Cryptic evolution]]~~	+
-	~~[[Category: Escherichia coli]]~~	+
-	~~[[Category: Oxa-48]]~~	+
-	~~[[Category: Resistance development]]~~	+
-	~~[[Category: Sub~~-~~mic~~]]	+

OCA at 07:46, 25 June 2021

OCA — Fri, 25 Jun 2021 07:46:03 GMT

←Older revision		Revision as of 07:46, 25 June 2021
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	==OXA-48_L67F_CAZ. What Doesnt Kill You Makes You Stronger: Sub-MIC Selection Drives Cryptic Evolution of OXA-48==		==OXA-48_L67F_CAZ. What Doesnt Kill You Makes You Stronger: Sub-MIC Selection Drives Cryptic Evolution of OXA-48==
-	<StructureSection load='7ass' size='340' side='right'caption='[[7ass]]' scene=''>	+	<StructureSection load='7ass' size='340' side='right'caption='[[7ass]], [[Resolution\|resolution]] 1.91Å' 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=7ASS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=7ASS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7ass]] is a 4 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=7ASS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ASS 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=7ass FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ass OCA], [~~http~~://pdbe.org/7ass PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7ass RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7ass PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7ass 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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=RYE:hydrolyzed+ceftazidime'>RYE</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">bla OXA-48, bla_2, bla_3, blaOXA-48, B6R99_29845, G5637_27540, GJJ01_28680, KPE71T_00045, SAMEA3649466_05396, SAMEA3673128_05462, SAMEA3729780_05587 ([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=7ass FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ass OCA], [https://pdbe.org/7ass PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ass RCSB], [https://www.ebi.ac.uk/pdbsum/7ass PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ass ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Our current understanding of how low antibiotic concentrations shape the evolution of contemporary beta-lactamases is limited. Using the widespread carbapenemase OXA-48, we tested the long-standing hypothesis that selective compartments with low antibiotic concentrations cause standing genetic diversity that could act as a gateway to developing clinical resistance. Here, we subjected Escherichia coli expressing bla OXA-48, on a clinical plasmid, to experimental evolution at sub-MICs of ceftazidime. We identified and characterized seven single variants of OXA-48. Susceptibility profiles and dose-response curves showed that they increased resistance only marginally. However, in competition experiments at sub-MICs of ceftazidime, they demonstrated strong selectable fitness benefits. Increased resistance was also reflected in elevated catalytic efficiencies toward ceftazidime. These changes are likely caused by enhanced flexibility of the Omega- and beta5-beta6 loops and fine-tuning of preexisting active site residues. In conclusion, low-level concentrations of beta-lactams can drive the evolution of beta-lactamases through cryptic phenotypes which may act as stepping-stones toward clinical resistance.IMPORTANCE Very low antibiotic concentrations have been shown to drive the evolution of antimicrobial resistance. While substantial progress has been made to understand the driving role of low concentrations during resistance development for different antimicrobial classes, the importance of beta-lactams, the most commonly used antibiotics, is still poorly studied. Here, we shed light on the evolutionary impact of low beta-lactam concentrations on the widespread beta-lactamase OXA-48. Our data indicate that the exposure to beta-lactams at very low concentrations enhances beta-lactamase diversity and drives the evolution of beta-lactamases by significantly influencing their substrate specificity. Thus, in contrast to high concentrations, low levels of these drugs may substantially contribute to the diversification and divergent evolution of these enzymes, providing a standing genetic diversity that can be selected and mobilized when antibiotic pressure increases.
		+
		+	Cryptic beta-Lactamase Evolution Is Driven by Low beta-Lactam Concentrations.,Frohlich C, Gama JA, Harms K, Hirvonen VHA, Lund BA, van der Kamp MW, Johnsen PJ, Samuelsen O, Leiros HS mSphere. 2021 Apr 28;6(2). pii: 6/2/e00108-21. doi: 10.1128/mSphere.00108-21. PMID:33910990<ref>PMID:33910990</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7ass" 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: Frohlich C]]	+	[[Category: Frohlich, C]]
-	[[Category: Leiros H-KS]]	+	[[Category: Leiros, H K.S]]
		+	[[Category: Antibiotic]]
		+	[[Category: Carbapenem]]
		+	[[Category: Carbapenemase]]
		+	[[Category: Ceftazidime]]
		+	[[Category: Collateral sensitivity]]
		+	[[Category: Cryptic evolution]]
		+	[[Category: Escherichia coli]]
		+	[[Category: Oxa-48]]
		+	[[Category: Resistance development]]
		+	[[Category: Sub-mic]]

OCA at 12:33, 16 December 2020

OCA — Wed, 16 Dec 2020 12:33:59 GMT

←Older revision		Revision as of 12:33, 16 December 2020
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-	'''Unreleased structure'''

-	~~The entry 7ass is ON HOLD until Paper Publication~~	+	==OXA-48_L67F_CAZ. What Doesnt Kill You Makes You Stronger: Sub-MIC Selection Drives Cryptic Evolution of OXA-48==
-		+	<StructureSection load='7ass' size='340' side='right'caption='[[7ass]]' scene=''>
-	~~Authors: Frohlich, C., Leiros, H.-K.S.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ASS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7ASS FirstGlance]. <br>
-	~~Description:~~ OXA-48_L67F_CAZ. What Doesnt Kill You Makes You Stronger: Sub-MIC Selection Drives Cryptic Evolution of OXA-48	+	</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=7ass FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ass OCA], [http://pdbe.org/7ass PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7ass RCSB], [http://www.ebi.ac.uk/pdbsum/7ass PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7ass ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Leiros~~, H.-K.S]]	+	__TOC__
-	[[Category: Frohlich, C]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Frohlich C]]
		+	[[Category: Leiros H-KS]]

OCA at 07:51, 18 November 2020

OCA — Wed, 18 Nov 2020 07:51:22 GMT

←Older revision		Revision as of 07:51, 18 November 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7ass is ON HOLD	+	The entry 7ass is ON HOLD until Paper Publication

	Authors: Frohlich, C., Leiros, H.-K.S.		Authors: Frohlich, C., Leiros, H.-K.S.

OCA: Protected "7ass" [edit=sysop:move=sysop]

OCA — Wed, 04 Nov 2020 05:24:30 GMT

Protected "7ass" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:24, 4 November 2020

OCA: New page: '''Unreleased structure''' The entry 7ass is ON HOLD Authors: Frohlich, C., Leiros, H.-K.S. Description: OXA-48_L67F_CAZ. What Doesnt Kill You Makes You Stronger: Sub-MIC Selection Dri...

OCA — Wed, 04 Nov 2020 05:24:28 GMT

New page: '''Unreleased structure''' The entry 7ass is ON HOLD Authors: Frohlich, C., Leiros, H.-K.S. Description: OXA-48_L67F_CAZ. What Doesnt Kill You Makes You Stronger: Sub-MIC Selection Dri...

New page

'''Unreleased structure'''

The entry 7ass is ON HOLD

Authors: Frohlich, C., Leiros, H.-K.S.

Description: OXA-48_L67F_CAZ. What Doesnt Kill You Makes You Stronger: Sub-MIC Selection Drives Cryptic Evolution of OXA-48
[[Category: Unreleased Structures]]
[[Category: Leiros, H.-K.S]]
[[Category: Frohlich, C]]