3D models of lamprey progesterone receptor complexed with progesterone, 7α-hydroxy-progesterone and 15α-hydroxy-progesterone

• Published in: Steroids 2011, Vol.76 (1), p.169-176
• Main Authors: Baker, Michael E., Asnaashari, Paiyuam, Chang, David J., McDonnell, Sunsanee
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Biological and medical sciences; Control of sea lamprey; Fundamental and applied biological sciences. Psychology; Humans; Lamprey progesterone receptor; Lampreys; Models, Molecular; Molecular Sequence Data; Progesterone - analogs & derivatives; Progesterone - chemistry; Progesterone receptor evolution; Receptors, Progesterone - chemistry; Sequence Alignment; Vertebrates: endocrinology
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2010.10.008

▶ 3D models of lamprey PR indicate that it can bind both 7α-OH-progesterone and 15α-OH-progesterone. ▶ Lamprey PR contains an important Met-277 that corresponds to Leu-887 on human PR. ▶ Methionine-277 on lamprey PR has a specific interaction with 15α-OH-progesterone. ▶ Lamprey PR could be a target for controlling reproduction of lamprey. Sea lamprey, a basal vertebrate, contains a progesterone receptor [PR]. An unusual property of lamprey is that gonadotropin-releasing hormone induces synthesis of 15α-hydroxy-progesterone [15α-OH-P] instead of progesterone. There also is indirect evidence for 7α-OH-P in lamprey serum. To determine if there is a structural basis for the binding of 7α-OH-P and 15α-OH-P to lamprey PR, we constructed 3D models of the lamprey PR complexed with progesterone, 7α-OH-P and 15α-OH-P. These 3D models reveal that Met-277 in lamprey PR has a specific interaction with the 15α-hydroxyl on 15α-OH-P and with Met-192, which also contacts the 15α-hydroxyl group. We also find that 7α-OH-P has favorable contacts with side-chains in lamprey PR. BLAST searches reveal that Met-277 on lamprey PR is unique among vertebrate PRs. This unique site on lamprey PR could be a target for compounds to control reproduction in sea lamprey, an environmental pest in Lake Michigan.