Words similar to penicillins
Example sentences for: penicillins
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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.
Generally, the S224A and S224K mutants exhibited small changes in K m and k cat , while the S224D mutant yielded 20- to 40-fold increased values for K m and >10-fold decreases in k cat when using the penicillins as substrates.
As with the I164A mutant, the changes in K m and k cat for the penicillins and carbapenems were relatively small, as compared with the values obtained with the cephalosporins (Table 4).
L1's preference for penicillins and carbapenems over cephalosporins, as exemplified by the k cat values, is in agreement with previous studies and supports L1's placement in the β-lactamase 3c family [ 9 ] .
Only when Ser224 was replaced with an Asp residue was there significant increases in the observed K m value for 6 of the 9 substrates tested, and the largest changes were exhibited when the penicillins were used as substrates.
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