1dht
From Proteopedia
(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 ...) |
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| - | [[Image:1dht.gif|left|200px]]<br /> | + | [[Image:1dht.gif|left|200px]]<br /><applet load="1dht" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1dht" size=" | + | |
caption="1dht, resolution 2.24Å" /> | caption="1dht, resolution 2.24Å" /> | ||
'''ESTROGENIC 17-BETA HYDROXYSTEROID DEHYDROGENASE COMPLEXED DIHYDROTESTOSTERONE'''<br /> | '''ESTROGENIC 17-BETA HYDROXYSTEROID DEHYDROGENASE COMPLEXED DIHYDROTESTOSTERONE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Steroid hormones share a very similar structure, but they behave | + | 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== | ==About this Structure== | ||
| - | 1DHT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with DHT as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Estradiol_17-beta-dehydrogenase Estradiol 17-beta-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62] Full crystallographic information is available from [http:// | + | 1DHT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=DHT:'>DHT</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Estradiol_17-beta-dehydrogenase Estradiol 17-beta-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DHT OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Campbell, R | + | [[Category: Campbell, R L.]] |
[[Category: Gangloff, A.]] | [[Category: Gangloff, A.]] | ||
[[Category: Han, Q.]] | [[Category: Han, Q.]] | ||
| - | [[Category: Lin, S | + | [[Category: Lin, S X.]] |
[[Category: DHT]] | [[Category: DHT]] | ||
[[Category: dht]] | [[Category: dht]] | ||
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[[Category: steroid]] | [[Category: steroid]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:16:41 2008'' |
Revision as of 10:16, 21 February 2008
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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 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
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