1jtv
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(New page: 200px<br /> <applet load="1jtv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jtv, resolution 1.54Å" /> '''Crystal structure o...)
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Revision as of 15:37, 12 November 2007
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Crystal structure of 17beta-Hydroxysteroid Dehydrogenase Type 1 complexed with Testosterone
Overview
Steroids are implicated in many physiological processes, such as, reproduction, aging, metabolism, and cancer. To understand the molecular, basis for steroid recognition and discrimination, we studied the human, estrogenic 17beta-hydroxysteroid dehydrogenase (17beta-HSD1) responsible, for the last step in the bioactivation of all estrogens. Here we report, the first observation of the conversion of dihydrotestosterone (DHT) into, 3beta,17beta-androstanediol (3beta-diol) by 17beta-HSD1, an estrogenic, enzyme studied for more than half a century. Kinetic observations, demonstrate that both the 3beta-reduction of DHT into 3beta-diol (kcat =, 0.040 s(-1)1; Km = 32 +/- 9 microM) and the 17beta-oxidation of DHT into, androstandione (A-dione) (kcat = 0.19 s(-1); Km = 26 +/-6 microM) are, catalyzed by 17beta-HSD1 via alternative binding orientation of the, steroid. The reduction of DHT was also observed in intact cells by using, HEK-293 cells stably transformed with 17beta-HSD1. The high-resolution, structure of a 17beta-HSD1-C19-steroid (testosterone) complex solved at, 1.54 A demonstrates that the steroid is reversibly oriented in the active, site, which strongly supports the existence of alternative binding mode., Such a phenomenon can be explained by the pseudo-symmetric structure of, C19-steroids. Our results confirm the role of the Leu149 residue in, C18/C19-steroid discrimination and suggest a possible mechanism of, 17beta-HSD1 in the modulation of DHT levels in tissues, such as the, breast, where both the enzyme and DHT are present.
About this Structure
1JTV is a Single protein structure of sequence from Homo sapiens with TES and GOL as ligands. Active as Estradiol 17-beta-dehydrogenase, with EC number 1.1.1.62 Full crystallographic information is available from OCA.
Reference
Pseudo-symmetry of C19 steroids, alternative binding orientations, and multispecificity in human estrogenic 17beta-hydroxysteroid dehydrogenase., Gangloff A, Shi R, Nahoum V, Lin SX, FASEB J. 2003 Feb;17(2):274-6. Epub 2002 Dec 17. PMID:12490543
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