Words similar to metallo-β-lactamases
Example sentences for: metallo-β-lactamases
How can you use “metallo-β-lactamases” in a sentence? Here are some example sentences to help you improve your vocabulary:
Two-thirds of all sequenced metallo-β-lactamases have an Asn at position 233 [ 41 ] , and this residue was predicted [ 42 ] and shown [ 43 ] to be involved with substrate binding and activation by interacting electrostatically with the substrate β-lactam carbonyl.
Efforts to solve the crystal structure of one of the metallo-β-lactamases with a bound substrate molecule have failed, most likely due to the high activity of the enzymes towards all β-lactam containing antibiotics [ 37 54 ] . Therefore, computational studies have been used extensively to study substrate binding, the role of the Zn(II) ions in catalysis, the protonation state of the active site, and inhibitor binding [ 37 42 55 56 57 58 59 ] . All of the substrate binding models have made assumptions before the substrate was docked into the active site [ 37 42 ] , and some of these assumptions have been shown to be invalid for certain substrates [ 43 ] . With L1, two key assumptions were made: (1) the bridging hydroxide functions as the nucleophile during catalysis and (2) Zn 1 coordinates the β-lactam carbonyl [ 37 ] . With these assumptions and after energy minimizations, Ser224 was predicted to hydrogen bond to the substrate carboxylate [ 37 ] , reminiscent of the role predicted for Lys224 in CcrA [ 42 ] . Ullah et al.
Instead, we predict that the insertion of an aspartic acid into the active site at position 224 results in a change in the hydrogen bonding network in L1; this hydrogen bonding network is extensive in all metallo-β-lactamases that have been characterized crystallographically [ 37 42 44 45 48 49 62 63 ] . The N233D mutant also exhibited greatly reduced k cat values for biapenem and meropenem but not for imipenem or any of the other substrates tested.
In order to prepare tight binding inhibitors of the metallo-β-lactamases, knowledge about how substrate binds to the enzymes is needed so that all substrate-enzyme binding contacts can be maintained in any proposed inhibitor.
The crystal structures of the metallo-β-lactamases reveal a complex and far-reaching hydrogen-bonding network around the metal binding sites, and disruption of this network is predicted to affect metal binding [ 37 42 44 45 48 49 62 63 ] . With all of the mutants described here except the S224K mutant, each mutant binds wild-type or near-wild-type levels of Zn(II) after purification.
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