Switching the Inhibitor-Enzyme Recognition Profile via Chimeric Carbonic Anhydrase XII.

ABSTRACT: A key part of the optimization of small molecules in pharmaceutical inhibitor development is to vary the molecular design to enhance complementarity of chemical features of the compound with the positioning of amino acids in the active site of a target enzyme. Typically this involves iterations of synthesis, to modify the compound, and biophysical assay, to assess the outcomes. Selective targeting of the anti-cancer carbonic anhydrase isoform XII (CA XII), this process is challenging because the overall fold is very similar across the twelve CA isoforms. To enhance drug development for CA XII we used a reverse engineering approach where mutation of the key six amino acids in the active site of human CA XII into the CA II isoform was performed to provide a protein chimera (chCA XII) which i

SUBMITTER: Smirnoviene J 

PROVIDER: S-EPMC8095314 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature