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| | {{STRUCTURE_1hdc| PDB=1hdc | SCENE= }} | | {{STRUCTURE_1hdc| PDB=1hdc | SCENE= }} |
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| - | '''MECHANISM OF INHIBITION OF 3ALPHA,20BETA-HYDROXYSTEROID DEHYDROGENASE BY A LICORICE-DERIVED STEROIDAL INHIBITOR'''
| + | ===MECHANISM OF INHIBITION OF 3ALPHA,20BETA-HYDROXYSTEROID DEHYDROGENASE BY A LICORICE-DERIVED STEROIDAL INHIBITOR=== |
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| - | ==Overview==
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| - | BACKGROUND: Bacterial 3 alpha, 20 beta-hydroxysteroid dehydrogenase (3 alpha, 20 beta-HSD) reversibly oxidizes the 3 alpha and 20 beta hydroxyl groups of androstanes and pregnanes and uses nicotinamide adenine dinucleotide as a cofactor. 3 alpha, 20 beta-HSD belongs to a family of short-chain dehydrogenases that has a highly conserved Tyr-X-X-X-Lys sequence. The family includes mammalian enzymes involved in hypertension, digestion, fertility and spermatogenesis. Several members of the enzyme family, including 3 alpha, 20 beta-HSD, are competitively inhibited by glycyrrhizic acid, a steroidal compound found in licorice, and its derivative, carbenoxolone, an anti-inflammatory glucocorticoid. RESULTS: The three-dimensional structure of the enzyme-carbenoxolone complex has been determined and refined at 2.2 A resolution to a crystallographic R-factor of 19.4%. The hemisuccinate side chain of carbenoxolone makes a hydrogen bond with the hydroxyl group of the conserved residue Tyr152 and occupies the position of the nicotinamide ring of the cofactor. The occupancies of the inhibitor in four independent catalytic sites refine to 100%, 95%, 54% and 36%. CONCLUSIONS: The steroid binds at the catalytic site in a mode much like the previously proposed mode of binding of the substrate cortisone. No bound cofactor molecules were found. The varying occupancy of steroid molecules observed in the four catalytic sites is either due to packing differences or indicates a cooperative effect among the four sites. The observed binding accounts for the inhibition of 3 alpha, 20 beta-HSD.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_7866748}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 7866748 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_7866748}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Ghosh, D.]] | | [[Category: Ghosh, D.]] |
| | [[Category: Oxidoreductase]] | | [[Category: Oxidoreductase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:43:39 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 08:01:39 2008'' |
Revision as of 05:01, 1 July 2008
Template:STRUCTURE 1hdc
MECHANISM OF INHIBITION OF 3ALPHA,20BETA-HYDROXYSTEROID DEHYDROGENASE BY A LICORICE-DERIVED STEROIDAL INHIBITOR
Template:ABSTRACT PUBMED 7866748
About this Structure
1HDC is a Single protein structure of sequence from Streptomyces exfoliatus. Full crystallographic information is available from OCA.
Reference
Mechanism of inhibition of 3 alpha, 20 beta-hydroxysteroid dehydrogenase by a licorice-derived steroidal inhibitor., Ghosh D, Erman M, Wawrzak Z, Duax WL, Pangborn W, Structure. 1994 Oct 15;2(10):973-80. PMID:7866748
Page seeded by OCA on Tue Jul 1 08:01:39 2008
