5lsc: Difference between revisions
From Proteopedia
Jump to navigationJump to search
New page: '''Unreleased structure''' The entry 5lsc is ON HOLD until sometime in the future Authors: Christopeit, T., Yang, K.-W., Yang, S.-K., Leiros, H.-K.S. Description: The structure of the ... |
No edit summary |
||
| (6 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
The | ==The structure of the metallo-beta-lactamase VIM-2 in complex with a triazolylthioacetamide inhibitor== | ||
<StructureSection load='5lsc' size='340' side='right'caption='[[5lsc]], [[Resolution|resolution]] 1.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5lsc]] 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=5LSC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LSC 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]] 1.497Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=752:2-[5-[2-(1,3-BENZOTHIAZOL-2-YLAMINO)-2-OXIDANYLIDENE-ETHYL]SULFANYL-4~{H}-1,2,4-TRIAZOL-3-YL]BENZOIC+ACID'>752</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=5lsc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lsc OCA], [https://pdbe.org/5lsc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lsc RCSB], [https://www.ebi.ac.uk/pdbsum/5lsc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lsc ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/B8QIQ9_PSEAI B8QIQ9_PSEAI] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The increasing number of pathogens expressing metallo-beta-lactamases (MBLs), and in this way achieving resistance to beta-lactam antibiotics, is a significant threat to global public health. A promising strategy to treat such resistant pathogens is the co-administration of MBL inhibitors together with beta-lactam antibiotics. However, an MBL inhibitor suitable for clinical use has not yet been identified. Verona integron-encoded metallo-beta-lactamase 2 (VIM-2) is a widespread MBL with a broad substrate spectrum and hence is an interesting drug target for the treatment of beta-lactam-resistant infections. In this study, three triazolylthioacetamides were tested as inhibitors of VIM-2. One of the tested compounds showed clear inhibition of VIM-2, with an IC50 of 20 microM. The crystal structure of the inhibitor in complex with VIM-2 was obtained by DMSO-free co-crystallization and was solved at a resolution of 1.50 A. To our knowledge, this is the first structure of a triazolylthioacetamide inhibitor in complex with an MBL. Analysis of the structure shows that the inhibitor binds to the two zinc ions in the active site of VIM-2 and revealed detailed information on the interactions involved. Furthermore, the crystal structure showed that binding of the inhibitor induced a conformational change of the conserved residue Trp87. | |||
The structure of the metallo-beta-lactamase VIM-2 in complex with a triazolylthioacetamide inhibitor.,Christopeit T, Yang KW, Yang SK, Leiros HK Acta Crystallogr F Struct Biol Commun. 2016 Nov 1;72(Pt 11):813-819. Epub 2016, Oct 24. PMID:27834790<ref>PMID:27834790</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5lsc" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Yang | <references/> | ||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Pseudomonas aeruginosa]] | |||
[[Category: Christopeit T]] | |||
[[Category: Leiros H-KS]] | |||
[[Category: Yang K-W]] | |||
[[Category: Yang S-K]] | |||
Latest revision as of 18:44, 18 October 2023
The structure of the metallo-beta-lactamase VIM-2 in complex with a triazolylthioacetamide inhibitor
| ||||||||||||
