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:
There are over 300 distinct β-lactamases known, and these enzymes have been grouped by a number of classification schemes [ 8 9 10 11 12 13 14 15 ] . For example, Bush has developed a scheme, based on the enzymes' molecular properties, that has four distinct β-lactamase groups [ 10 15 ] . One of the more alarming groups are the Bush group 3 enzymes, which are Zn(II) dependent enzymes that hydrolyze nearly all known β-lactam containing antibiotics and for which there are no or very few known clinical inhibitors [ 9 14 16 17 18 19 ] . The metallo-β-lactamases have been further divided by Bush into subgroups based on amino acid sequence identity: the Ba enzymes share a >23% sequence identity, require 2 Zn(II) ions for full activity, prefer penicillins and cephalosporins as substrates, and are represented by metallo-β-lactamase CcrA from Bacteroides fragilis, the Bb enzymes share a 11% sequence identity with the Ba enzymes, require only 1 Zn(II) ion for full activity, prefer carbapenems as substrates, and are represented by the metallo-β-lactamase imiS from Aeromonas sobria, and the Bc enzymes have only 9 conserved residues with the other metallo-β-lactamases, require 2 Zn(II) ions for activity, contain a different metal binding motif than the other metallo-β-lactamases, prefer penicillins as substrates, and are represented by the metallo-β-lactamase L1 from Stenotrophomonas maltophilia [ 9 ] . A similar grouping scheme (B1, B2, and B3) based on structural properties of the metallo-β-lactamases has recently been offered [ 41 ] . The diversity of the group 3 β-lactamases is best exemplified by the enzymes' vastly differing efficacies towards non-clinical inhibitors; these differences predict that one inhibitor may not inhibit all metallo-β-lactamases [ 18 20 21 22 23 24 25 26 27 28 29 ] . To combat this problem, we are characterizing a metallo-β-lactamase from each of the subgroups in an effort to identify a common structural or mechanistic aspect of the enzymes that can be targeted for the generation of an inhibitor.
However, MJ0301 has been shown to belong to the metallo-β-lactamase superfamily of enzymes and, in the evolutionary classification of metallo-β-lactamases, belongs to an archaea-specific family (Figure 2; COG1237) [ 28].
All sequenced subclass Ba and Bb metallo-β-lactamases (except VIM-1) have a lysine residue at position 224 [ 41 ] , and all computational models for substrate binding to the metallo-β-lactamases assume that the invariant carboxylate on substrates forms an electrostatic interaction with this lysine.
All crystallographically characterized metallo-β-lactamases have a flexible amino acid chain that extends over the active site [ 37 42 44 45 46 47 48 49 ] . Previous NMR studies on CcrA have shown that this loop "clamps down" on substrate or inhibitor upon binding, and there is speculation that the distortion of substrate upon clamping down of the loop may drive catalysis [ 50 ] . The crystal structure of L1 showed that there is a large loop that extends over the active site, and modeling studies have predicted that two residues, Ile164 and Phe158, make significant contacts with large, hydrophobic substituents at the 2' or 6' positions on penicillins, cephalosporins, or carbapenems [ 37 ] . To test this prediction, Ile 164 and Phe158 were changed from large, hydrophobic residues to alanines to afford the I164A and F158A mutants.
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.
Loading...