5hh4 - Revision history

OCA at 11:21, 3 January 2024

OCA — Wed, 03 Jan 2024 11:21:11 GMT

←Older revision		Revision as of 11:21, 3 January 2024
Line 3:		Line 3:
	<StructureSection load='5hh4' size='340' side='right'caption='[[5hh4]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='5hh4' size='340' side='right'caption='[[5hh4]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5hh4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~"bacillus_marcescens"_(bizio_1823)_trevisan_in_de_toni_and_trevisan_1889 "bacillus~~ marcescens~~" (bizio 1823) trevisan in de toni and trevisan 1889~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HH4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5hh4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Serratia_marcescens Serratia marcescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HH4 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=60M:6-(PHOSPHONOMETHYL)PYRIDINE-2-CARBOXYLIC+ACID'>60M</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 2Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=60M:6-(PHOSPHONOMETHYL)PYRIDINE-2-CARBOXYLIC+ACID'>60M</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=5hh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hh4 OCA], [https://pdbe.org/5hh4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hh4 RCSB], [https://www.ebi.ac.uk/pdbsum/5hh4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hh4 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=5hh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hh4 OCA], [https://pdbe.org/5hh4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hh4 RCSB], [https://www.ebi.ac.uk/pdbsum/5hh4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hh4 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/BLAB_SERMA BLAB_SERMA]] Confers resistance to imipenem and broad-spectrum beta-lactams. Also hydrolyzes carbapenems.	+	[https://www.uniprot.org/uniprot/BLAB_SERMA BLAB_SERMA] Confers resistance to imipenem and broad-spectrum beta-lactams. Also hydrolyzes carbapenems.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Beta-lactamase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Hinchliffe, P~~]]	+	[[Category: Serratia marcescens]]
-	[[Category: ~~Spencer, J~~]]	+	[[Category: Hinchliffe P]]
-	[[Category: ~~Antibiotic resistance]]~~	+	[[Category: Spencer J]]
-	~~[[Category: Carbapenamase]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Phosphonate]]~~	+
-	~~[[Category: Pyridine~~]]	+

OCA at 10:54, 30 March 2022

OCA — Wed, 30 Mar 2022 10:54:25 GMT

←Older revision		Revision as of 10:54, 30 March 2022
Line 1:		Line 1:

	==Crystal structure of metallo-beta-lactamase IMP-1 in complex with a phosphonate-based inhibitor==		==Crystal structure of metallo-beta-lactamase IMP-1 in complex with a phosphonate-based inhibitor==
-	<StructureSection load='5hh4' size='340' side='right' caption='[[5hh4]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='5hh4' size='340' side='right'caption='[[5hh4]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5hh4]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/"bacillus_marcescens"_(bizio_1823)_trevisan_in_de_toni_and_trevisan_1889 "bacillus marcescens" (bizio 1823) trevisan in de toni and trevisan 1889]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HH4 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5HH4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5hh4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_marcescens"_(bizio_1823)_trevisan_in_de_toni_and_trevisan_1889 "bacillus marcescens" (bizio 1823) trevisan in de toni and trevisan 1889]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HH4 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=60M:6-(PHOSPHONOMETHYL)PYRIDINE-2-CARBOXYLIC+ACID'>60M</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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" id="ligandDat"><scene name='pdbligand=60M:6-(PHOSPHONOMETHYL)PYRIDINE-2-CARBOXYLIC+ACID'>60M</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5hh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hh4 OCA], [~~http~~://pdbe.org/5hh4 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5hh4 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5hh4 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5hh4 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=5hh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hh4 OCA], [https://pdbe.org/5hh4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hh4 RCSB], [https://www.ebi.ac.uk/pdbsum/5hh4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hh4 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/BLAB_SERMA BLAB_SERMA]] Confers resistance to imipenem and broad-spectrum beta-lactams. Also hydrolyzes carbapenems.	+	[[https://www.uniprot.org/uniprot/BLAB_SERMA BLAB_SERMA]] Confers resistance to imipenem and broad-spectrum beta-lactams. Also hydrolyzes carbapenems.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 21:

	==See Also==		==See Also==
-	*[[Beta-lactamase\|Beta-lactamase]]	+	*[[Beta-lactamase 3D structures\|Beta-lactamase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 27:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Beta-lactamase]]		[[Category: Beta-lactamase]]
		+	[[Category: Large Structures]]
	[[Category: Hinchliffe, P]]		[[Category: Hinchliffe, P]]
	[[Category: Spencer, J]]		[[Category: Spencer, J]]

OCA at 15:48, 27 February 2019

OCA — Wed, 27 Feb 2019 15:48:45 GMT

←Older revision		Revision as of 15:48, 27 February 2019
Line 3:		Line 3:
	<StructureSection load='5hh4' size='340' side='right' caption='[[5hh4]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='5hh4' size='340' side='right' caption='[[5hh4]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5hh4]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HH4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HH4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5hh4]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_marcescens"_(bizio_1823)_trevisan_in_de_toni_and_trevisan_1889 "bacillus marcescens" (bizio 1823) trevisan in de toni and trevisan 1889]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HH4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HH4 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=60M:6-(PHOSPHONOMETHYL)PYRIDINE-2-CARBOXYLIC+ACID'>60M</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=60M:6-(PHOSPHONOMETHYL)PYRIDINE-2-CARBOXYLIC+ACID'>60M</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></td></tr>
Line 10:		Line 10:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/BLAB_SERMA BLAB_SERMA]] Confers resistance to imipenem and broad-spectrum beta-lactams. Also hydrolyzes carbapenems.		[[http://www.uniprot.org/uniprot/BLAB_SERMA BLAB_SERMA]] Confers resistance to imipenem and broad-spectrum beta-lactams. Also hydrolyzes carbapenems.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	There are currently no clinically available inhibitors of metallo-beta-lactamases (MBLs), enzymes that hydrolyze beta-lactam antibiotics and confer resistance to Gram-negative bacteria. Here we present 6-phosphonomethylpyridine-2-carboxylates (PMPCs) as potent inhibitors of subclass B1 (IMP-1, VIM-2, and NDM-1) and B3 (L1) MBLs. Inhibition followed a competitive, slow-binding model without an isomerization step (IC50 values of 0.3-7.2 muM; Ki values of 0.03-1.5 muM). Minimum inhibitory concentration assays demonstrated potentiation of beta-lactam (Meropenem) activity against MBL-producing bacteria, including clinical isolates, at concentrations at which eukaryotic cells remain viable. Crystal structures revealed unprecedented modes of binding of inhibitor to B1 (IMP-1) and B3 (L1) MBLs. In IMP-1, binding does not replace the nucleophilic hydroxide, and the PMPC carboxylate and pyridine nitrogen interact closely (2.3 and 2.7 A, respectively) with the Zn2 ion of the binuclear metal site. The phosphonate group makes limited interactions but is 2.6 A from the nucleophilic hydroxide. Furthermore, the presence of a water molecule interacting with the PMPC phosphonate and pyridine N-C2 pi-bond, as well as the nucleophilic hydroxide, suggests that the PMPC binds to the MBL active site as its hydrate. Binding is markedly different in L1, with the phosphonate displacing both Zn2, forming a monozinc enzyme, and the nucleophilic hydroxide, while also making multiple interactions with the protein main chain and Zn1. The carboxylate and pyridine nitrogen interact with Ser221 and -223, respectively (3 A distance). The potency, low toxicity, cellular activity, and amenability to further modification of PMPCs indicate these and similar phosphonate compounds can be further considered for future MBL inhibitor development.
		+
		+	Structural and Kinetic Studies of the Potent Inhibition of Metallo-beta-lactamases by 6-Phosphonomethylpyridine-2-carboxylates.,Hinchliffe P, Tanner CA, Krismanich AP, Labbe G, Goodfellow VJ, Marrone L, Desoky AY, Calvopina K, Whittle EE, Zeng F, Avison MB, Bols NC, Siemann S, Spencer J, Dmitrienko GI Biochemistry. 2018 Mar 27;57(12):1880-1892. doi: 10.1021/acs.biochem.7b01299., Epub 2018 Mar 9. PMID:29485857<ref>PMID:29485857</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5hh4" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Beta-lactamase\|Beta-lactamase]]		*[[Beta-lactamase\|Beta-lactamase]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 06:57, 6 October 2017

OCA — Fri, 06 Oct 2017 06:57:50 GMT

←Older revision		Revision as of 06:57, 6 October 2017
Line 10:		Line 10:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/BLAB_SERMA BLAB_SERMA]] Confers resistance to imipenem and broad-spectrum beta-lactams. Also hydrolyzes carbapenems.		[[http://www.uniprot.org/uniprot/BLAB_SERMA BLAB_SERMA]] Confers resistance to imipenem and broad-spectrum beta-lactams. Also hydrolyzes carbapenems.
		+
		+	==See Also==
		+	*[[Beta-lactamase\|Beta-lactamase]]
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 00:40, 19 January 2017

OCA — Thu, 19 Jan 2017 00:40:36 GMT

←Older revision		Revision as of 00:40, 19 January 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 5hh4 is ON HOLD until Paper Publication~~	+	==Crystal structure of metallo-beta-lactamase IMP-1 in complex with a phosphonate-based inhibitor==
-		+	<StructureSection load='5hh4' size='340' side='right' caption='[[5hh4]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~Authors: Hinchliffe, P., Spencer, J.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5hh4]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HH4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HH4 FirstGlance]. <br>
-	~~Description:~~ Crystal structure of metallo-beta-lactamase IMP-1 in complex with a phosphonate-based inhibitor	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=60M:6-(PHOSPHONOMETHYL)PYRIDINE-2-CARBOXYLIC+ACID'>60M</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5hh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hh4 OCA], [http://pdbe.org/5hh4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hh4 RCSB], [http://www.ebi.ac.uk/pdbsum/5hh4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hh4 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/BLAB_SERMA BLAB_SERMA]] Confers resistance to imipenem and broad-spectrum beta-lactams. Also hydrolyzes carbapenems.
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Beta-lactamase]]
		+	[[Category: Hinchliffe, P]]
	[[Category: Spencer, J]]		[[Category: Spencer, J]]
-	[[Category: ~~Hinchliffe, P~~]]	+	[[Category: Antibiotic resistance]]
		+	[[Category: Carbapenamase]]
		+	[[Category: Hydrolase]]
		+	[[Category: Inhibitor]]
		+	[[Category: Phosphonate]]
		+	[[Category: Pyridine]]

OCA: Protected "5hh4" [edit=sysop:move=sysop]

OCA — Wed, 20 Jan 2016 15:25:27 GMT

Protected "5hh4" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:25, 20 January 2016

OCA: New page: '''Unreleased structure''' The entry 5hh4 is ON HOLD until Paper Publication Authors: Hinchliffe, P., Spencer, J. Description: Crystal structure of metallo-beta-lactamase IMP-1 in comp...

OCA — Wed, 20 Jan 2016 15:25:25 GMT

New page: '''Unreleased structure''' The entry 5hh4 is ON HOLD until Paper Publication Authors: Hinchliffe, P., Spencer, J. Description: Crystal structure of metallo-beta-lactamase IMP-1 in comp...

New page

'''Unreleased structure'''

The entry 5hh4 is ON HOLD until Paper Publication

Authors: Hinchliffe, P., Spencer, J.

Description: Crystal structure of metallo-beta-lactamase IMP-1 in complex with a phosphonate-based inhibitor
[[Category: Unreleased Structures]]
[[Category: Spencer, J]]
[[Category: Hinchliffe, P]]