Table 2.
Summary of the structure-function information available for the VIM-1 variants.
Variant | Closest variant for reference |
Mutation(s) of interest |
Localization | Comments a |
---|---|---|---|---|
VIM-2 | VIM-1 | H224Y | ASL10 | Increased affinity for ceftazidime (KM value of 98 vs. 794 μM), compared to VIM-1 [40, 108]. |
VIM-31 | VIM-2 | Y224H | ASL10 | Overall decreased activity (e.g. ampicillin: 0.9 vs. 1.4 μM−1 s−1; ceftazidime: 0.005 vs. 0.05 μM−1 s−1; meropenem: 0.3 vs. 2.5 μM−1 s−1), compared to VIM-2 [113]. |
VIM-4 VIM-13 VIM-19 VIM-23 |
VIM-1 | S228R | ASL10 | Decreased activity for extended-spectrum cephalosporins, compared to VIM-1 (e.g. cefepime: 0.03 vs. 0.4 μM−1 s−1, for VIM-13 and VIM-1, respectively [117]). |
VIM-11 | VIM-2 | N165S | Near ASL10 | Increased activity for ceftazidime (0.13 vs. 0.03 μM−1 s−1); cefepime (0.083 vs. 0.03 μM−1 s−1); and cefpirome (0.6 vs. 0.28 μM−1 s−1), compared to VIM-2 [119]. |
S60K F61L |
Enlarged active-site cavity, likely due to increased flexibility of ASL3 and loss of H- bonding at ASL10. Overall decreased activity for most cephalosporins (e.g. cephalothin: 4 vs. 12 μM−1 s−1; ceftazidime: 0.012 vs. 0.05 μM−1 s−1; cefotaxime: 2.6 vs. 5.8 μM−1 s−1), compared to VIM-2 [171]. |
|||
D62G | ASL3 | |||
VIM-7 | VIM-2 | G63D | ||
A64T | ||||
S68P | ||||
Y224H | ASL10 | |||
Y218P |
Based on kcat/KM values, unless noted.