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==Carbapenemase VCC-1 from Vibrio cholerae N14-02106== | ==Carbapenemase VCC-1 from Vibrio cholerae N14-02106== | ||
<StructureSection load='6mk6' size='340' side='right' caption='[[6mk6]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='6mk6' size='340' side='right' caption='[[6mk6]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6mk6]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MK6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MK6 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6mk6]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillo_virgola_del_koch"_trevisan_1884 "bacillo virgola del koch" trevisan 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MK6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MK6 FirstGlance]. <br> | ||
</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> | </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=6mk6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mk6 OCA], [http://pdbe.org/6mk6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mk6 RCSB], [http://www.ebi.ac.uk/pdbsum/6mk6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mk6 ProSAT]</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=6mk6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mk6 OCA], [http://pdbe.org/6mk6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mk6 RCSB], [http://www.ebi.ac.uk/pdbsum/6mk6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mk6 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In 2016 we identified a new class A carbapenemase, VCC-1, in nontoxigenic Vibrio cholerae that had been isolated from retail shrimp imported into Canada for human consumption. Shortly thereafter, seven additional VCC-1 producing V. cholerae were isolated along the German coastline. These isolates appear to have acquired the VCC-1 gene (bla VCC-1) independently from the Canadian isolate, suggesting bla VCC-1 is mobile and widely distributed. VCC-1 hydrolyzes penicillins, cephalothin, aztreonam, and carbapenems, and like the broadly disseminated class A carbapenemase KPC-2, is only weakly inhibited by clavulanic acid or tazobactam. Although VCC-1 has yet to observed in the clinic, its encroachment into aquaculture and other areas with human activity suggests the enzyme may be emerging as a public health threat. To pre-emptively address this threat, we examined the structural and functional biology of VCC-1 against the FDA approved non-beta-lactam-based inhibitor avibactam. We found that avibactam restored the in vitro sensitivity of V. cholerae to meropenem, impenem and ertapenem. Acylation efficiency was lower for VCC-1 as compared to KPC-2 and akin to that of Pseudomonas aeruginosa PAO1 AmpC (k2/Ki=3.0 x 10(3) M(-1)sec(-137)). The tertiary structure of VCC-1 is similar to that of KPC-2 and they bind avibactam similarly; however, our analyses suggest that VCC-1 may be unable to degrade avibactam as has been found for KPC-2. Based on our prior genomics-based surveillance, we were able to target VCC-1 for detailed molecular studies to gain early insights that could be used to combat this carbapenemse in the future. | |||
Molecular basis for the potent inhibition of the emerging carbapenemase VCC-1 by avibactam.,Mangat CS, Vadlamani G, Holicek V, Chu M, Larmour V, Vocadlo DJ, Mulvey MR, Mark BL Antimicrob Agents Chemother. 2019 Feb 19. pii: AAC.02112-18. doi:, 10.1128/AAC.02112-18. PMID:30782990<ref>PMID:30782990</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6mk6" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacillo virgola del koch trevisan 1884]] | |||
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Mark, B L]] | [[Category: Mark, B L]] | ||