1jtv: Difference between revisions

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[[Image:1jtv.gif|left|200px]]
{{Seed}}
[[Image:1jtv.png|left|200px]]


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{{STRUCTURE_1jtv|  PDB=1jtv  |  SCENE=  }}  
{{STRUCTURE_1jtv|  PDB=1jtv  |  SCENE=  }}  


'''Crystal structure of 17beta-Hydroxysteroid Dehydrogenase Type 1 complexed with Testosterone'''
===Crystal structure of 17beta-Hydroxysteroid Dehydrogenase Type 1 complexed with Testosterone===




==Overview==
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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.
The line below this paragraph, {{ABSTRACT_PUBMED_12490543}}, adds the Publication Abstract to the page
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{{ABSTRACT_PUBMED_12490543}}


==About this Structure==
==About this Structure==
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[[Category: Alternative binding mode]]
[[Category: Alternative binding mode]]
[[Category: Steroid hormone]]
[[Category: Steroid hormone]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 21:54:51 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 20:50:50 2008''

Revision as of 17:50, 1 July 2008

File:1jtv.png

Template:STRUCTURE 1jtv

Crystal structure of 17beta-Hydroxysteroid Dehydrogenase Type 1 complexed with Testosterone

Template:ABSTRACT PUBMED 12490543

About this Structure

1JTV is a Single protein structure of sequence from Homo sapiens. 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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