A MOLECULAR-MODEL OF THE INDUCER BINDING DOMAIN OF THE GALACTOSE REPRESSOR OF ESCHERICHIA-COLI

The C-terminal inducer binding domain of the Escherichia coli galactos e repressor (GalR) is homologous to several periplasmic chemoreceptor proteins whose three-dimensional structures have been determined at hi gh resolution (Vyas, N. K., Vyas, M. N., and Quiocho, F. A. (1991) J. Biol. Chem. 266, 5226-5237; Mowbray, S. L. and Cole, L. B. (1992) J. M ol. Biol. 225, 155-175). The protein backbone was constructed from the coordinates of glucose/galactose-binding protein using the Homology p rogram (Biosym Technologies, San Diego). Loops were built by searching for substructures in the structure data base, and the side chains wer e built using a rotamer-based program. A small amount of energy minimi zation relieved steric strain within the model. The GalR model that ha s been constructed is consistent with the principles of protein struct ure; values obtained for the compactness and buried surface area of th e model compare favorably with those determined for the chemoreceptor protein structures. The model is consistent with, and provides structu ral interpretations for, experimental results obtained from physical a nd biochemical studies. Predictions are made concerning the residues c onferring the specificity of galactose induction of GalR and for self association to dimers. The model provides a first step toward correlat ing the structure and regulation of GalR and in determining the chemis try of its homologous and heterologous interactions that are critical to its role as a regulator of transcription initiation.