1dht
From Proteopedia
OCA (Talk | contribs)
(New page: 200px<br /> <applet load="1dht" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dht, resolution 2.24Å" /> '''ESTROGENIC 17-BETA ...)
Next diff →
Revision as of 14:26, 12 November 2007
|
ESTROGENIC 17-BETA HYDROXYSTEROID DEHYDROGENASE COMPLEXED DIHYDROTESTOSTERONE
Overview
Steroid hormones share a very similar structure, but they behave, distinctly. We present structures of human estrogenic, 17beta-hydroxysteroid dehydrogenase (17beta-HSD1) complexes with, dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT), providing the, first pictures to date of DHEA and DHT bound to a protein. Comparisons of, these structures with that of the enzyme complexed with the most potent, estrogen, estradiol, revealed the structural basis and general model for, sex hormone recognition and discrimination. Although the binding cavity is, almost entirely composed of hydrophobic residues that can make only, nonspecific interactions, the arrangement of residues is highly, complementary to that of the estrogenic substrate. Relatively small, changes in the shape of the steroid hormone can significantly affect the, binding affinity and specificity. The K(m) of estrone is more than, 1000-fold lower than that of DHEA and the K(m) of estradiol is about 10, times lower than that of DHT. The structures suggest that Leu-149 is the, primary contributor to the discrimination of C-19 steroids and estrogens, by 17beta-HSD1. The critical role of Leu-149 has been well confirmed by, site-directed mutagenesis experiments, as the Leu-149 --> Val variant, showed a significantly decreased K(m) for C-19 steroids while losing, discrimination between estrogens and C-19 steroids. The electron density, of DHEA also revealed a distortion of its 17-ketone toward a beta-oriented, form, which approaches the transition-state conformation for DHEA, reduction.
About this Structure
1DHT is a Single protein structure of sequence from Homo sapiens with DHT as ligand. Active as Estradiol 17-beta-dehydrogenase, with EC number 1.1.1.62 Full crystallographic information is available from OCA.
Reference
Dehydroepiandrosterone and dihydrotestosterone recognition by human estrogenic 17beta-hydroxysteroid dehydrogenase. C-18/c-19 steroid discrimination and enzyme-induced strain., Han Q, Campbell RL, Gangloff A, Huang YW, Lin SX, J Biol Chem. 2000 Jan 14;275(2):1105-11. PMID:10625652
Page seeded by OCA on Mon Nov 12 16:32:43 2007
