3D models of lamprey progesterone receptor complexed with progesterone, 7alpha-hydroxy-progesterone and 15alpha-hydroxy-progesterone
Sea lamprey, a basal vertebrate, contains a progesterone receptor [PR]. An unusual property of lamprey is that gonadotropin-releasing hormone induces synthesis of 15alpha-hydroxy-progesterone [15alpha-OH-P] instead of progesterone. There also is indirect evidence for 7alpha-OH-P in lamprey serum. To determine if there is a structural basis for the binding of 7alpha-OH-P and 15alpha-OH-P to lamprey PR, we constructed 3D models of the lamprey PR complexed with progesterone, 7alpha-OH-P and 15alpha-OH-P. These 3D models reveal that Met-277 in lamprey PR has a specific interaction with the 15alpha-hydroxyl on 15alpha-OH-P and with Met-192, which also contacts the 15alpha-hydroxyl group. We also find that 7alpha-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.
Steroids. 2011 Jan;76(1-2):169-76. doi: 10.1016/j.steroids.2010.10.008. Epub 2010 Nov 3.
