STEROIDS, STEROID-BINDING PROTEINS AND HYDROPHOBIC BINDING-SITES

Dorothy Crowfoot's first research assignment was to work on steroid st ructure, a controversial subject when she started her research. She co mpleted this assignment in 1945 with the first three-dimensional struc ture of a steroid molecule, cholesteryl iodide. More recently, the str uctures of proteins which bind steroids have been determined. Some of them have a large closed cavity, big enough for the steroid nucleus, f illed with up to 13 molecules of ordered water which must be displaced when a steroid is bound. Even more extensive arrays of ordered water molecules are observed in the binding cavity of some fatty acid-bindin g proteins. It is suggested that the function of these arrays of order ed water is to enhance the free energy released when a hydrophobic sub strate is bound to them. This creates a favourable equilibrium which a llows the enzymes to draw in these substrate molecules from their exis ting hydrophobic environment in micelles or membranes.