6dja: Difference between revisions

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'''Unreleased structure'''


The entry 6dja is ON HOLD
==ZN-DEPENDENT 5/B/6 METALLO-BETA-LACTAMASE FROM BACILLUS CEREUS==
<StructureSection load='6dja' size='340' side='right'caption='[[6dja]], [[Resolution|resolution]] 2.48&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6dja]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_cereus Bacillus cereus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DJA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DJA 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]] 2.48&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=6dja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dja OCA], [https://pdbe.org/6dja PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dja RCSB], [https://www.ebi.ac.uk/pdbsum/6dja PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dja ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BLAB_BACCE BLAB_BACCE] Confers resistance to the different beta-lactams antibiotics (penicillin, cephalosporin and carbapenem) via the hydrolysis of the beta-lactam ring. Benzylpenicillin is a better substrate than cephalosporin C and ampicillin (PubMed:3131315, PubMed:2501295).<ref>PMID:1904717</ref> <ref>PMID:2501295</ref> <ref>PMID:3131315</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The hydrolysis of beta-lactam antibiotics by beta-lactamase enzymes is the most prominent antibiotic resistance mechanism for many pathogenic bacteria. Out of this broad class of enzymes, metallo-beta-lactamases are of special clinical interest because of their broad substrate specificities. Several in vitro inhibitors for various metallo-beta-lactamases have been reported with no clinical efficacy. Previously, we described a 10-nucleotide single stranded DNA aptamer (10-mer) that inhibits Bacillus cereus 5/B/6 metallo-beta-lactamase very effectively. Here, we find that the aptamer shows uncompetitive inhibition of Bacillus cereus 5/B/6 metallo-beta-lactamase during cefuroxime hydrolysis. To understand the mechanism of inhibition, we report a 2.5 A resolution X-ray crystal structure and solution-state NMR analysis of the free enzyme. Chemical shift perturbations were observed in the HSQC spectra for several residues upon titrating with increasing concentrations of the 10-mer. In the X-ray crystal structure, these residues are distal to the active site, suggesting an allosteric mechanism for the aptamer inhibition of the enzyme. HADDOCK molecular docking simulations suggest that the 10-mer docks 26 A from the active site. We then mutated the three lysine residues in the basic binding patch to glutamine and measured the catalytic activity and inhibition by the 10-mer. No significant inhibition of these mutants was observed by the 10-mer as compared to wild type. Interestingly, mutation of Lys50 (Lys78; according to standard MBL numbering system) resulted in reduced enzymatic activity relative to wild type in the absence of inhibitor, further highlighting an allosteric mechanism for inhibition.


Authors: Bui, A.A., Khan, N.H., Shaw, R.W., Sutton, R.B.
A DNA aptamer reveals an allosteric site for inhibition in metallo-beta-lactamases.,Khan NH, Bui AA, Xiao Y, Sutton RB, Shaw RW, Wylie BJ, Latham MP PLoS One. 2019 Apr 22;14(4):e0214440. doi: 10.1371/journal.pone.0214440., eCollection 2019. PMID:31009467<ref>PMID:31009467</ref>


Description: ZN-DEPENDENT 5/B/6 METALLO-BETA-LACTAMASE FROM BACILLUS CEREUS
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Sutton, R.B]]
<div class="pdbe-citations 6dja" style="background-color:#fffaf0;"></div>
[[Category: Bui, A.A]]
 
[[Category: Khan, N.H]]
==See Also==
[[Category: Shaw, R.W]]
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacillus cereus]]
[[Category: Large Structures]]
[[Category: Bui AA]]
[[Category: Khan NH]]
[[Category: Shaw RW]]
[[Category: Sutton RB]]
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