LexA repressor and iron uptake regulator from Escherichia coli: new members of the CAP-like DNA binding domain superfamily.

Comparison of structures can reveal surprising connections between protein families and provide new insights into the relationship between sequence, structure and function. The solution structure of LexA repressor from Escherichia coli reveals an unexpected structural similarity to a widespread class of prokaryotic and eukaryotic regulatory proteins, which is typified by catabolite gene activator protein (CAP). The use of combined sequence profiles allows the identification of two new prokaryotic members of the superfamily: listeriolysin regulatory protein (PrfA) and ferric uptake regulatory protein (Fur). LexA, PrfA and Fur are the first examples of prokaryotic regulatory proteins in which DNA recognition is mediated by a variant of the classical helix-turn-helix motif, with an insertion in the turn region.