5n5i - Revision history

OCA at 18:03, 8 November 2023

OCA — Wed, 08 Nov 2023 18:03:18 GMT

←Older revision		Revision as of 18:03, 8 November 2023
Line 1:		Line 1:

	==Crystal Structure of VIM-1 metallo-beta-lactamase in complex with hydrolysed meropenem==		==Crystal Structure of VIM-1 metallo-beta-lactamase in complex with hydrolysed meropenem==
-	<StructureSection load='5n5i' size='340' side='right' caption='[[5n5i]], [[Resolution\|resolution]] 2.20Å' scene=''>	+	<StructureSection load='5n5i' size='340' side='right'caption='[[5n5i]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5n5i]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N5I OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5N5I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5n5i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N5I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N5I FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LMP:(2~{S},3~{R},4~{S})-2-[(2~{S},3~{R})-1,3-BIS(OXIDANYL)-1-OXIDANYLIDENE-BUTAN-2-YL]-4-[(3~{S},5~{S})-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL-3-METHYL-3,4-DIHYDRO-2~{H}-PYRROLE-5-CARBOXYLIC+ACID'>LMP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.2Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">blaVIM, blaVIM-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 "Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LMP:(2~{S},3~{R},4~{S})-2-[(2~{S},3~{R})-1,3-BIS(OXIDANYL)-1-OXIDANYLIDENE-BUTAN-2-YL]-4-[(3~{S},5~{S})-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL-3-METHYL-3,4-DIHYDRO-2~{H}-PYRROLE-5-CARBOXYLIC+ACID'>LMP</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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5n5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n5i OCA], [~~http~~://pdbe.org/5n5i PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5n5i RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5n5i PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5n5i 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=5n5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n5i OCA], [https://pdbe.org/5n5i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n5i RCSB], [https://www.ebi.ac.uk/pdbsum/5n5i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n5i ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q9XAY4_PSEAI Q9XAY4_PSEAI]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 21:

	==See Also==		==See Also==
-	*[[Beta-lactamase\|Beta-lactamase]]	+	*[[Beta-lactamase 3D structures\|Beta-lactamase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Hinchliffe, P~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Salimraj, R~~]]	+	[[Category: Pseudomonas aeruginosa]]
-	[[Category: ~~Spencer, J~~]]	+	[[Category: Hinchliffe P]]
-	[[Category: ~~Antibiotic~~]]	+	[[Category: Salimraj R]]
-	[[Category: ~~Carbapenemase]]~~	+	[[Category: Spencer J]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Lactamase]]~~	+
-	~~[[Category: Meropenem~~]]	+

OCA at 15:50, 27 February 2019

OCA — Wed, 27 Feb 2019 15:50:25 GMT

←Older revision		Revision as of 15:50, 27 February 2019
Line 3:		Line 3:
	<StructureSection load='5n5i' size='340' side='right' caption='[[5n5i]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='5n5i' size='340' side='right' caption='[[5n5i]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5n5i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N5I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5N5I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5n5i]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N5I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5N5I FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LMP:(2~{S},3~{R},4~{S})-2-[(2~{S},3~{R})-1,3-BIS(OXIDANYL)-1-OXIDANYLIDENE-BUTAN-2-YL]-4-[(3~{S},5~{S})-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL-3-METHYL-3,4-DIHYDRO-2~{H}-PYRROLE-5-CARBOXYLIC+ACID'>LMP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LMP:(2~{S},3~{R},4~{S})-2-[(2~{S},3~{R})-1,3-BIS(OXIDANYL)-1-OXIDANYLIDENE-BUTAN-2-YL]-4-[(3~{S},5~{S})-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL-3-METHYL-3,4-DIHYDRO-2~{H}-PYRROLE-5-CARBOXYLIC+ACID'>LMP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">blaVIM, blaVIM-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 "Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885])</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=5n5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n5i OCA], [http://pdbe.org/5n5i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n5i RCSB], [http://www.ebi.ac.uk/pdbsum/5n5i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n5i 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=5n5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n5i OCA], [http://pdbe.org/5n5i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n5i RCSB], [http://www.ebi.ac.uk/pdbsum/5n5i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n5i ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Metallo-beta-Lactamases (MBLs) protect bacteria from almost all beta-lactam antibiotics. Verona integron-encoded MBL (VIM) enzymes are among the most clinically important MBLs, with VIM-1 increasing in carbapenem-resistant Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae) that are among the hardest bacterial pathogens to treat. VIM enzymes display sequence variation at residues (224 and 228) that in related MBLs are conserved and participate in substrate binding. How they accommodate this variability, while retaining catalytic efficiency against a broad substrate range, has remained unclear. Here, we present crystal structures of VIM-1 and its complexes with a substrate-mimicking thioenolate inhibitor, ML302F, that restores meropenem activity against a range of VIM-1 producing clinical strains, and the hydrolysed product of the carbapenem meropenem. Comparison of these two structures identifies a water-mediated hydrogen bond, between the carboxylate group of substrate/inhibitor and the backbone carbonyl of the active site zinc ligand Cys221, that is common to both complexes. Structural comparisons show that the responsible Cys221-bound water is observed in all known VIM structures, participates in carboxylate binding with other inhibitor classes, and thus effectively replicates the role of the conserved Lys224 in analogous complexes with other MBLs. These results provide a mechanism for substrate binding that permits the variation at positions 224 and 228 that is a hallmark of VIM MBLs. ENZYMES: EC 3.5.2.6 DATABASES: Co-ordinates and structure factors for protein structures described in this manuscript have been deposited in the Protein Data Bank (www.rcsb.org/pdb) with accession codes 5N5G (VIM-1), 5N5H (VIM-1:ML302F complex) and 5N5I (VIM-1-hydrolysed meropenem complex).
		+
		+	Crystal structures of VIM-1 complexes explain active site heterogeneity in VIM-class metallo-beta-lactamases.,Salimraj R, Hinchliffe P, Kosmopoulou M, Tyrrell JM, Brem J, van Berkel SS, Verma A, Owens RJ, McDonough MA, Walsh TR, Schofield CJ, Spencer J FEBS J. 2019 Jan;286(1):169-183. doi: 10.1111/febs.14695. Epub 2018 Nov 23. PMID:30430727<ref>PMID:30430727</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5n5i" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta-lactamase\|Beta-lactamase]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 04:58, 8 March 2018

OCA — Thu, 08 Mar 2018 04:58:07 GMT

←Older revision		Revision as of 04:58, 8 March 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 5n5i is ON HOLD until Paper Publication~~	+	==Crystal Structure of VIM-1 metallo-beta-lactamase in complex with hydrolysed meropenem==
-		+	<StructureSection load='5n5i' size='340' side='right' caption='[[5n5i]], [[Resolution\|resolution]] 2.20Å' scene=''>
-	~~Authors: Salimraj, R., Hinchliffe, P., Spencer, J.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5n5i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N5I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5N5I FirstGlance]. <br>
-	~~Description:~~ Crystal Structure of VIM-1 metallo-beta-lactamase in complex with hydrolysed meropenem	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LMP:(2~{S},3~{R},4~{S})-2-[(2~{S},3~{R})-1,3-BIS(OXIDANYL)-1-OXIDANYLIDENE-BUTAN-2-YL]-4-[(3~{S},5~{S})-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL-3-METHYL-3,4-DIHYDRO-2~{H}-PYRROLE-5-CARBOXYLIC+ACID'>LMP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<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=5n5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n5i OCA], [http://pdbe.org/5n5i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n5i RCSB], [http://www.ebi.ac.uk/pdbsum/5n5i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n5i ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Spencer~~, J]]	+	</table>
		+	__TOC__
		+	</StructureSection>
	[[Category: Hinchliffe, P]]		[[Category: Hinchliffe, P]]
	[[Category: Salimraj, R]]		[[Category: Salimraj, R]]
		+	[[Category: Spencer, J]]
		+	[[Category: Antibiotic]]
		+	[[Category: Carbapenemase]]
		+	[[Category: Hydrolase]]
		+	[[Category: Lactamase]]
		+	[[Category: Meropenem]]

OCA: Protected "5n5i" [edit=sysop:move=sysop]

OCA — Thu, 09 Mar 2017 12:05:23 GMT

Protected "5n5i" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:05, 9 March 2017

OCA: New page: '''Unreleased structure''' The entry 5n5i is ON HOLD until Paper Publication Authors: Salimraj, R., Hinchliffe, P., Spencer, J. Description: Crystal Structure of VIM-1 metallo-beta-lac...

OCA — Thu, 09 Mar 2017 12:05:21 GMT

New page: '''Unreleased structure''' The entry 5n5i is ON HOLD until Paper Publication Authors: Salimraj, R., Hinchliffe, P., Spencer, J. Description: Crystal Structure of VIM-1 metallo-beta-lac...

New page

'''Unreleased structure'''

The entry 5n5i is ON HOLD until Paper Publication

Authors: Salimraj, R., Hinchliffe, P., Spencer, J.

Description: Crystal Structure of VIM-1 metallo-beta-lactamase in complex with hydrolysed meropenem
[[Category: Unreleased Structures]]
[[Category: Spencer, J]]
[[Category: Hinchliffe, P]]
[[Category: Salimraj, R]]