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| - | [[Image:1jtv.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1jtv| PDB=1jtv | SCENE= }} | | {{STRUCTURE_1jtv| PDB=1jtv | SCENE= }} |
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| - | '''Crystal structure of 17beta-Hydroxysteroid Dehydrogenase Type 1 complexed with Testosterone'''
| + | ===Crystal structure of 17beta-Hydroxysteroid Dehydrogenase Type 1 complexed with Testosterone=== |
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| - | ==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 |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 12490543 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_12490543}} |
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| | ==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
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
Page seeded by OCA on Tue Jul 1 20:50:50 2008
