Predicted structure of the sugar-binding site of the lac repressor

The lactose repressor protein from Escherichia coli binds sugars, primarily galactosides, which modulate its interactions with operator DNA and thereby affect synthesis of the lac metabolic enzymes. The affinity of the repressor for operator DNA is decreased by binding inducer sugars and increased by binding anti-inducer sugars. Based on regions of the primary structure implicated by genetic methods to be involved in sugar binding, amino acid sequence homology between L-arabinose-binding protein (ABP) and lac repressor has recently been reported. The sugar-binding sites for these two proteins might be expected to have similar structural features, as both bind L-arabinose and D-galactose. The high resolution structure of ABP reported in the accompanying article provides complete definition of amino acids in the sugar-binding site. By identification of homologous residues in the lac repressor, we have now predicted the structure of the portion of the repressor sugar-binding site which accommodates the galactosyl moiety. This prediction provides the first potential view of the inducer/anti-inducer site in the repressor protein.