View source for 5zgf


==Crystal structure of NDM-1 Q123G mutant==
<StructureSection load='5zgf' size='340' side='right'caption='[[5zgf]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5zgf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZGF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZGF 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]] 1.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OH:HYDROXIDE+ION'>OH</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=5zgf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zgf OCA], [https://pdbe.org/5zgf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zgf RCSB], [https://www.ebi.ac.uk/pdbsum/5zgf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zgf ProSAT]</span></td></tr>
</table>
== Function ==
[https://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 ==
Beta-lactam antibiotics are the mainstay for the treatment of bacterial infections. However, elevated resistance to these antibiotics mediated by metallo-beta-lactamases (MBL) has become a global concern. New Delhi metallo-beta-lactamase-1 (NDM-1), a newly added member of the MBL family that can hydrolyze almost all beta-lactam antibiotics, has rapidly spread all over the world and posed serious clinical threats. Broad-spectrum and mechanism-based inhibitors against all MBLs are highly desired, but the differential mechanisms of MBLs towards different antibiotics pose a great challenge. To facilitate the design of mechanism-based inhibitors, we investigated the active-site conformational changes of NDM-1 through the determination of a series of 15 high-resolution crystal structures in native form and in complex with products, biochemical and biophysical studies, site-directed mutagenesis and molecular dynamics computation. The structural studies reveal the consistency of the active site conformations in NDM-1/products complexes and the fluctuation in native NDM-1 structures. The enzymatic measurements indicate a correlation between enzymatic activity and the active site fluctuation with more fluctuation favoring higher activity. This correlation is further validated by structural and enzymatic studies of the Q123G mutant. Our combinational studies suggest that active site conformational fluctuation promotes the enzymatic activity of NDM-1, which may guide further mechanism studies and inhibitor design.

Active site conformational fluctuations promote the enzymatic activity of NDM-1.,Zhang H, Ma G, Zhu Y, Zeng L, Ahmad A, Wang C, Pang B, Fang H, Zhao L, Hao Q Antimicrob Agents Chemother. 2018 Aug 27. pii: AAC.01579-18. doi:, 10.1128/AAC.01579-18. PMID:30150473<ref>PMID:30150473</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5zgf" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Klebsiella pneumoniae]]
[[Category: Large Structures]]
[[Category: Hao Q]]
[[Category: Zhang H]]