%0 Journal Article %J Steroids %D 2011 %T 3D models of lamprey progesterone receptor complexed with progesterone, 7alpha-hydroxy-progesterone and 15alpha-hydroxy-progesterone %A Baker, M. E. %A Asnaashari, P. %A Chang, D. J. %A McDonnell, S. %K & %K Amino Acid Sequence %K Animals %K derivatives/ chemistry %K Humans %K Lampreys %K Models %K Molecular %K Molecular Sequence Data %K Progesterone/ analogs %K Progesterone/ chemistry %K Receptors %K Sequence Alignment %X

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.

%B Steroids %7 2010/11/09 %V 76 %P 169-76 %8 Jan %@ 1878-5867 (Electronic)00 %G eng