cover illustration The ligand binding specificity of the human estrogen receptor a (hERα) was altered so that it would recognize the non-steroidal synthetic compound (CV3220). Because of the structural similarities of 17ß-estradiol (E2) and CV3220, molecular docking studies predicted that CV3220 is positioned into the ligand binding pocket of hERa similar to E2. However, it activates the receptor only at 10 000 fold higher ligand concentrations. After iterative rounds of site specific saturation mutagenesis of a fixed set of residues within 4.6 Å of CV3320 and subsequent random mutagenesis of the ligand binding pocket, a mutant receptor was generated that showed a 67-fold increased activity CV3320 and a 10-fold decreased activity to E2. For further details please see Islam et al., pp. 45-52.
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