3-DIMENSIONAL STRUCTURES OF STEROIDS AND THEIR PROTEIN TARGETS

Steroid receptors and enzymes that control steroid synthesis and metab olism work together to control vital hormonal functions. Crystallograp hic data on steroids having high affinity for estrogen, progestin, and corticoid receptors suggest that receptor binding is primarily the re sult of a high level of complementarity between the receptor and the s teroidal A-ring. The crystal structures of two steroid dehydrogenase e nzymes reveal the location of the active site, the position of the con served catalytic triad (Tyr-Lys-Ser), a possible mechanism of keto-hyd roxyl interconversion and the basis for selectivity. A complex between carbenoxolone and one of the enzymes reveals how the active ingredien t in licorice inhibits this enzyme as well as human 11 beta-hydroxyste roid dehydrogenase (11 beta-HSD). The complex reveals that the inhibit or fills tile substrate binding pocket, displaces the cofactor and acc epts a hydrogen bond from a tyrosine residue, one of less than 20 stri ctly conserved residues in the family of enzymes, explaining how inges tion of licorice can produce hypertension.