3D models of lamprey progesterone receptor complexed with progesterone, 7α-hydroxy-progesterone and 15α-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 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.
Department of Medicine, 0693, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0693, USA. mbaker@ucsd.edu
Michael E
ME
Baker
Paiyuam
P
Asnaashari
David J
DJ
Chang
Sunsanee
S
McDonnell
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D007798:Lampreys; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011374:Progesterone / Q000031:analogs & derivatives* / Q000737:chemistry*; D011980:Receptors, Progesterone / Q000737:chemistry*; D016415:Sequence Alignment
D011980:Receptors, Progesterone; D011374:Progesterone