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==Crystal Structure of the Mono-Zinc Metallo-beta-lactamase VIM-4 from Pseudomonas aeruginosa== | |||
<StructureSection load='2wrs' size='340' side='right'caption='[[2wrs]], [[Resolution|resolution]] 2.79Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2wrs]] is a 2 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=2WRS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WRS 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]] 2.79Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</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=2wrs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wrs OCA], [https://pdbe.org/2wrs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wrs RCSB], [https://www.ebi.ac.uk/pdbsum/2wrs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wrs ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q70E11_PSEAI Q70E11_PSEAI] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wr/2wrs_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2wrs ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Although commercialized inhibitors of active site serine beta-lactamases are currently used in coadministration with antibiotic therapy, no clinically useful inhibitors of metallo-beta-lactamases (MBLs) have yet been discovered. In this paper, we investigated the inhibitory effect of mercaptophosphonate derivatives against the three subclasses of MBLs (B1, B2, and B3). All 14 tested mercaptophosphonates, with the exception of 1a, behaved as competitive inhibitors for the three subclasses. Apart from 13 and 21, all the mercaptophosphonates tested exhibit a good inhibitory effect on the subclass B2 MBL CphA with low inhibition constants (K(i) < 15 muM). Interestingly, compound 18 turned out to be a potent broad spectrum MBL inhibitor. The crystallographic structures of the CphA-10a and CphA-18 complexes indicated that the sulfur atom of 10a and the phosphonato group of 18 interact with the Zn(2+) ion, respectively. Molecular modeling studies of the interactions between compounds 10a and 18 and the VIM-4 (B1), CphA (B2), and FEZ-1 (B3) enzymes brought to light different binding modes depending on the enzyme and the inhibitor, consistent with the crystallographic structures. | |||
Mercaptophosphonate Compounds as Broad-Spectrum Inhibitors of the Metallo-beta-lactamases.,Lassaux P, Hamel M, Gulea M, Delbruck H, Mercuri PS, Horsfall L, Dehareng D, Kupper M, Frere JM, Hoffmann K, Galleni M, Bebrone C J Med Chem. 2010 Jun 8. PMID:20527888<ref>PMID:20527888</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2wrs" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Beta-lactamase|Beta-lactamase]] | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Pseudomonas aeruginosa]] | [[Category: Pseudomonas aeruginosa]] | ||
[[Category: Bebrone | [[Category: Bebrone C]] | ||
[[Category: Dehareng | [[Category: Dehareng D]] | ||
[[Category: Delbruck | [[Category: Delbruck H]] | ||
[[Category: Ferrer | [[Category: Ferrer J-L]] | ||
[[Category: Frere | [[Category: Frere J-M]] | ||
[[Category: Galleni | [[Category: Galleni M]] | ||
[[Category: Gaumont | [[Category: Gaumont A-C]] | ||
[[Category: Gulea | [[Category: Gulea M]] | ||
[[Category: Hamel | [[Category: Hamel M]] | ||
[[Category: Hoffmann | [[Category: Hoffmann K]] | ||
[[Category: Horsfall | [[Category: Horsfall L]] | ||
[[Category: Lassaux | [[Category: Lassaux P]] | ||
[[Category: Mercuri | [[Category: Mercuri PS]] | ||
[[Category: Traore | [[Category: Traore DAK]] | ||
Latest revision as of 13:14, 20 December 2023
Crystal Structure of the Mono-Zinc Metallo-beta-lactamase VIM-4 from Pseudomonas aeruginosaCrystal Structure of the Mono-Zinc Metallo-beta-lactamase VIM-4 from Pseudomonas aeruginosa
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAlthough commercialized inhibitors of active site serine beta-lactamases are currently used in coadministration with antibiotic therapy, no clinically useful inhibitors of metallo-beta-lactamases (MBLs) have yet been discovered. In this paper, we investigated the inhibitory effect of mercaptophosphonate derivatives against the three subclasses of MBLs (B1, B2, and B3). All 14 tested mercaptophosphonates, with the exception of 1a, behaved as competitive inhibitors for the three subclasses. Apart from 13 and 21, all the mercaptophosphonates tested exhibit a good inhibitory effect on the subclass B2 MBL CphA with low inhibition constants (K(i) < 15 muM). Interestingly, compound 18 turned out to be a potent broad spectrum MBL inhibitor. The crystallographic structures of the CphA-10a and CphA-18 complexes indicated that the sulfur atom of 10a and the phosphonato group of 18 interact with the Zn(2+) ion, respectively. Molecular modeling studies of the interactions between compounds 10a and 18 and the VIM-4 (B1), CphA (B2), and FEZ-1 (B3) enzymes brought to light different binding modes depending on the enzyme and the inhibitor, consistent with the crystallographic structures. Mercaptophosphonate Compounds as Broad-Spectrum Inhibitors of the Metallo-beta-lactamases.,Lassaux P, Hamel M, Gulea M, Delbruck H, Mercuri PS, Horsfall L, Dehareng D, Kupper M, Frere JM, Hoffmann K, Galleni M, Bebrone C J Med Chem. 2010 Jun 8. PMID:20527888[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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