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| - | [[Image:1bhs.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1bhs| PDB=1bhs | SCENE= }} | | {{STRUCTURE_1bhs| PDB=1bhs | SCENE= }} |
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| - | '''HUMAN ESTROGENIC 17BETA-HYDROXYSTEROID DEHYDROGENASE'''
| + | ===HUMAN ESTROGENIC 17BETA-HYDROXYSTEROID DEHYDROGENASE=== |
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| - | ==Overview==
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| - | BACKGROUND: The principal human estrogen, 17 beta-estradiol, is a potent stimulator of certain endocrine-dependent forms of breast cancer. Because human estrogenic 17 beta-hydroxysteroid dehydrogenase (type I 17 beta-HSD) catalyzes the last step in the biosynthesis of 17 beta-estradiol from the less potent estrogen, estrone, it is an attractive target for the design of inhibitors of estrogen production and tumor growth. This human enzyme shares less than 15% sequence identity with a bacterial 3 alpha,20 beta-HSD, for which the three-dimensional structure is known. The amino acid sequence of 17 beta-HSD also differs from that of bacterial 3 alpha,20 beta-HSD by two insertions (of 11 and 14 residues) and 52 additional residues at the C terminus. RESULTS: The 2.20 A resolution structure of type I 17 beta-HSD, the first mammalian steroidogenic enzyme studied by X-ray crystallographic techniques, reveals a fold characteristic of the short-chain dehydrogenases. The active site contains a Tyr-X-X-X-Lys sequence (where X is any amino acid) and a serine residue, features that are conserved in short-chain steroid dehydrogenases. The structure also contains three alpha-helices and a helix-turn-helix motif, not observed in short-chain dehydrogenase structures reported previously. No cofactor density could be located. CONCLUSIONS: The helices present in 17 beta-HSD that were not in the two previous short-chain dehydrogenase structures are located at one end of the substrate-binding cleft away from the catalytic triad. These helices restrict access to the active site and appear to influence substrate specificity. Modeling the position of estradiol in the active site suggests that a histidine side chain may play a critical role in substrate recognition. One or more of these helices may also be involved in the reported association of the enzyme with membranes. A model for steroid and cofactor binding as well as for the estrone to estradiol transition state is proposed. The structure of the active site provides a rational basis for designing more specific inhibitors of this breast cancer associated enzyme.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_7663947}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 7663947 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_7663947}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Short-chain dehydrogenase]] | | [[Category: Short-chain dehydrogenase]] |
| | [[Category: Steroid dehydrogenase]] | | [[Category: Steroid dehydrogenase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:31:51 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 19:11:22 2008'' |
Revision as of 16:11, 30 June 2008
Template:STRUCTURE 1bhs
HUMAN ESTROGENIC 17BETA-HYDROXYSTEROID DEHYDROGENASE
Template:ABSTRACT PUBMED 7663947
About this Structure
1BHS is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of human estrogenic 17 beta-hydroxysteroid dehydrogenase at 2.20 A resolution., Ghosh D, Pletnev VZ, Zhu DW, Wawrzak Z, Duax WL, Pangborn W, Labrie F, Lin SX, Structure. 1995 May 15;3(5):503-13. PMID:7663947
Page seeded by OCA on Mon Jun 30 19:11:22 2008
