6MKQ
Carbapenemase VCC-1 bound to avibactam
Summary for 6MKQ
| Entry DOI | 10.2210/pdb6mkq/pdb |
| Descriptor | Beta-lactamase, (2S,5R)-1-formyl-5-[(sulfooxy)amino]piperidine-2-carboxamide (3 entities in total) |
| Functional Keywords | carbapenemase, vcc-1, avibactam, beta-lactamase, vibrio cholerae, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Vibrio cholerae |
| Total number of polymer chains | 1 |
| Total formula weight | 29497.16 |
| Authors | Mark, B.L.,Vadlamani, G. (deposition date: 2018-09-26, release date: 2019-01-30, Last modification date: 2023-10-11) |
| Primary citation | Mangat, C.S.,Vadlamani, G.,Holicek, V.,Chu, M.,Larmour, V.L.C.,Vocadlo, D.J.,Mulvey, M.R.,Mark, B.L. Molecular Basis for the Potent Inhibition of the Emerging Carbapenemase VCC-1 by Avibactam. Antimicrob. Agents Chemother., 63:-, 2019 Cited by PubMed Abstract: In 2016, we identified a new class A carbapenemase, VCC-1, in a nontoxigenic strain that had been isolated from retail shrimp imported into Canada for human consumption. Shortly thereafter, seven additional VCC-1-producing isolates were recovered along the German coastline. These isolates appear to have acquired the VCC-1 gene () independently from the Canadian isolate, suggesting that 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 be observed in the clinic, its encroachment into aquaculture and other areas with human activity suggests that the enzyme may be emerging as a public health threat. To preemptively address this threat, we examined the structural and functional biology of VCC-1 against the FDA-approved non-β-lactam-based inhibitor avibactam. We found that avibactam restored the sensitivity of to meropenem, imipenem, and ertapenem. The acylation efficiency was lower for VCC-1 than for KPC-2 and akin to that of PAO1 AmpC (/ = 3.0 × 10 M s). 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 carbapenemase in the future. PubMed: 30782990DOI: 10.1128/AAC.02112-18 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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