6dja
From Proteopedia
(Difference between revisions)
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<StructureSection load='6dja' size='340' side='right'caption='[[6dja]], [[Resolution|resolution]] 2.48Å' scene=''> | <StructureSection load='6dja' size='340' side='right'caption='[[6dja]], [[Resolution|resolution]] 2.48Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6dja]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DJA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6dja]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_14579 Atcc 14579]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DJA FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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='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> | ||
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== Function == | == Function == | ||
[[http://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> | [[http://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. | ||
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| + | 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> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6dja" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Atcc 14579]] | ||
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
Revision as of 17:54, 11 December 2019
ZN-DEPENDENT 5/B/6 METALLO-BETA-LACTAMASE FROM BACILLUS CEREUS
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Categories: Atcc 14579 | Beta-lactamase | Large Structures | Bui, A A | Khan, N H | Shaw, R W | Sutton, R B | Hydrolase | Lactamase | Zinc
