The fascinating complexities of steroid-binding enzymes.
Enzymes that modulate the level of circulating steroid hormone can be used to combat steroid-dependent disorders. Members of the NADPH-dependent short chain dehydrogenase/reductase (SDR) family control blood pressure, fertility, and natural and neoplastic growth. Despite the fact that only one amino acid residue is strictly conserved in the 60 known members of the family, all appear to have the dinucleotide-binding Rossmann fold and homologous catalytic residues containing the conserved tyrosine. Variation in the amino acid composition of the substrate binding pocket creates specificity of binding for steroids, prostaglandins, sugars and alcohols. Licorice induces high blood pressure by inhibiting an SDR in the kidney, and appears to combat ulcers by inhibiting another in the stomach. Detailed X-ray analyses of various members of the family should allow the design of potent, tissue-specific, highly selective inhibitors.
Duax
W L
WL
Hauptman-Woodward Medical Research Institute, Buffalo, NY 14203, USA. duax@hwi.buffalo.edu
Griffin
J F
JF
Ghosh
D
D
D000595:Amino Acid Sequence; D004798:Enzymes / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009243:NAD / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013256:Steroids / Q000378:metabolism*; D013379:Substrate Specificity
D004798:Enzymes; D013256:Steroids; D009243:NAD