Department of Medicine, 0693, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0693, USA.
Steroids. 2011 Jan;76(1-2):169-76. doi: 10.1016/j.steroids.2010.10.008. Epub 2010 Nov 3.
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.
海七鳃鳗是一种基干脊椎动物，含有孕激素受体[PR]。七鳃鳗的一个不寻常特性是促性腺激素释放激素诱导 15α-羟孕酮[15α-OH-P]的合成，而不是孕激素。七鳃鳗血清中也有 7α-OH-P 的间接证据。为了确定 7α-OH-P 和 15α-OH-P 与七鳃鳗 PR 结合是否有结构基础，我们构建了与孕激素、7α-OH-P 和 15α-OH-P 结合的七鳃鳗 PR 的 3D 模型。这些 3D 模型表明，七鳃鳗 PR 中的 Met-277 与 15α-OH-P 的 15α-羟基和与 15α-羟基基团接触的 Met-192 具有特定的相互作用。我们还发现 7α-OH-P 与七鳃鳗 PR 中的侧链有良好的接触。BLAST 搜索表明，七鳃鳗 PR 上的 Met-277 在脊椎动物 PR 中是独一无二的。七鳃鳗 PR 上的这个独特位点可能是控制密歇根湖环境害虫海七鳃鳗生殖的化合物的靶标。
