View source for 6ibv


==Crystal structure of NDM-1 beta-lactamase in complex with broad spectrum boronic inhibitor cpd 1==
<StructureSection load='6ibv' size='340' side='right'caption='[[6ibv]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ibv]] is a 2 chain structure with sequence from [http://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=6IBV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IBV FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=H9E:[5-(bromomethyl)-1-benzothiophen-2-yl]-tris(oxidanyl)boranuide'>H9E</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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">blaNDM-1 ([http://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'>[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=6ibv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ibv OCA], [http://pdbe.org/6ibv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ibv RCSB], [http://www.ebi.ac.uk/pdbsum/6ibv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ibv ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/BLAN1_KLEPN BLAN1_KLEPN]] Confers resistance to many beta-lactam antibiotics, including some carbapenems. Does not confer resistance to the polymixin colistin or the fluoroquinolone ciprofloxacin. 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Recent decades have witnessed a dramatic increase of multidrug resistant (MDR) bacteria, compromising the efficacy of available antibiotics, and a continual decline in the discovery of novel antibacterials. We recently reported the first library of benzo[b]thiophen-2-ylboronic acid inhibitors sharing broad spectrum activity against beta-lactamases (BLs). The ability of these compounds to inhibit structurally and mechanistically different types of beta-lactamases has been here structurally investigated. An extensive X-ray crystallographic analysis of boronic acids (BAs) binding to proteins representative of serine BLs (SBLs) and metallo beta-lactamases (MBLs) have been conducted to depict the role played by the boronic group in driving molecular recognition, especially in the interaction with MBLs. Our derivatives are the first case of noncyclic boronic acids active against MBLs and represent a productive route toward potent broad-spectrum inhibitors.

X-ray Crystallography Deciphers the Activity of Broad-Spectrum Boronic Acid beta-Lactamase Inhibitors.,Cendron L, Quotadamo A, Maso L, Bellio P, Montanari M, Celenza G, Venturelli A, Costi MP, Tondi D ACS Med Chem Lett. 2019 Mar 27;10(4):650-655. doi:, 10.1021/acsmedchemlett.8b00607. eCollection 2019 Apr 11. PMID:30996812<ref>PMID:30996812</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ibv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Beta-lactamase]]
[[Category: Large Structures]]
[[Category: Bellio, P]]
[[Category: Celenza, G]]
[[Category: Cendron, L]]
[[Category: Costi, M P]]
[[Category: Maso, L]]
[[Category: Montanari, M]]
[[Category: Quotadamo, A]]
[[Category: Tondi, D]]
[[Category: Venturelli, A]]
[[Category: Acyclic boronic inhibitor]]
[[Category: Bacterial resistance]]
[[Category: Hydrolase]]