title: Crystal structures of 11β-hydroxysteroid dehydrogenase type 1 and their use in drug discovery.
abstract: Cortisol is synthesized by 11β-hydroxysteroid dehydrogenase type 1, inhibitors of which may treat disease associated with excessive cortisol levels. The crystal structures of 11β-hydroxysteroid dehydrogenase type 1 that have been released may aid drug discovery. The crystal structures have been analyzed in terms of the interactions between the protein and the ligands. Despite a variety of structurally different inhibitors the crystal structures of the proteins are quite similar. However, the differences are significant for drug discovery. The crystal structures can be of use in drug discovery, but care needs to be taken when selecting structures for use in virtual screening and ligand docking.
authors: Medicinal Chemistry, Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
authors: Mark P
authors: MP
authors: Thomas
authors: Barry V L
authors: BV
authors: Potter
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray / Q000379:methods*; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D018086:Glutamate Dehydrogenase (NADP+) / Q000737:chemistry / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D006860:Hydrogen Bonding; D008024:Ligands; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000201:enzymology*; D051379:Mice; D008958:Models, Molecular; D011487:Protein Conformation; D051381:Rats
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D018086:Glutamate Dehydrogenase (NADP+); D006854:Hydrocortisone