Abstract
Numerous steroids are essential plant, animal, and human hormones. The medical and industrial applications of these hormones require the identification of new synthetic routes, including biotransformations. The metabolic fate of a steroid can be complicated; it may be transformed into a variety of substituted derivatives. This may be because a steroid molecule can adopt several possible orientations in the binding pocket of a receptor or an enzyme. The present study, based on docking and molecular dynamics, shows that it is indeed possible for a steroid molecule to bind to a receptor binding site in two or more orientations (normal, head-to-tail reversed, upside down). Three steroids were considered: progesterone, dehydroepiandrosterone, and 7-oxo-dehydroepiandrosterone. Two proteins were employed as hosts: the human mineralocorticoid receptor and a bacterial Baeyer–Villiger monooxygenase. When the steroids were in nonstandard orientations, the estimated binding strength was found to be only moderately diminished and the network of hydrogen bonds between the steroid and the host was preserved.
Highlights
Steroid hormones and their derivatives form a large group of useful pharmaceutical preparations that are employed in the prevention and treatment of diverse diseases in gynecology, endocrinology, rheumatology, oncology, etc
We report on the docked structures of these three steroid ligands, their relative energies, as well as the dynamic behavior of the steroids in the binding pockets of the receptors
For DHEA and 7-oxo-DHEA, the best docked structures are again very similar to the experimental orientation of progesterone; the corresponding root mean square deviation (RMSD) is 0.39 Å for both DHEA and 7-oxo-DHEA. Some of this increase in RMSD for DHEA and 7-oxo-DHEA compared to progesterone can be attributed to differences in the steroid nuclei of these ligands
Summary
Steroid hormones and their derivatives form a large group of useful pharmaceutical preparations that are employed in the prevention and treatment of diverse diseases in gynecology, endocrinology, rheumatology, oncology, etc. They are used medically and industrially because numerous steroids are essential plant, animal, and human hormones. Medical and industrial applications of this class of compounds require the identification of new synthetic routes, preferably using cheap starting materials (e.g., phytosterols). Such routes include biotransformations, which are ecologically friendlier and more stereospecific synthetic pathways than chemical derivatization [2]. Side-chain degradation involves four groups of inducible enzymes: the fatty acid β-oxidation, ω-oxidase reaction, methyl-crotonyl-CoA carboxylation, and propionyl-CoA
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
