The present invention provides altered lac repressor proteins that
recognize the lactose operator with increased affinity and have either
normal or enhanced ligand responsivity. For example, the lac repressor
Gln60Gly mutant protein exhibits increased binding affinity for lactose
operator DNA, while maintaining near-normal responsivity to IPTG.
Alternatively, the present invention provides modified repressors which
exhibit responsiveness to an alternative ligand, such as arabinose, or
have enhanced responsivity to IPTG. For example, Gln60Gly/Leu148Phe binds
with wild-type affinity to lactose operator DNA and exhibits enhanced
responsivity to IPTG. The present invention also provides for repressors
that exhibit both characteristics: increased affinity for lactose
operator and enhanced ligand responsivity. Enhanced ligand response
enables induction of gene expression to be finely controlled by a
researcher. DNA sequences encoding the altered lac repressor proteins and
bacterial and eukaryotic cells containing altered lac repressor proteins
are also provided.