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| {{STRUCTURE_1fdw| PDB=1fdw | SCENE= }} | | {{STRUCTURE_1fdw| PDB=1fdw | SCENE= }} |
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| '''HUMAN 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE 1 MUTANT H221Q COMPLEXED WITH ESTRADIOL'''
| | ===HUMAN 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE 1 MUTANT H221Q COMPLEXED WITH ESTRADIOL=== |
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| ==Overview==
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| Type 1 17beta-hydroxysteroid dehydrogenase (17beta-HSD1), a member of the short chain dehydrogenase reductase (SDR) family, is responsible for the synthesis of 17beta-estradiol, the biologically active estrogen involved in the genesis and development of human breast cancers. Here, we report the crystal structures of the H221L 17beta-HSD1 mutant complexed to NADP+ and estradiol and the H221L mutant/NAD+ and a H221Q mutant/estradiol complexes. These structures provide a complete picture of the NADP+-enzyme interactions involving the flexible 191-199 loop (well ordered in the H221L mutant) and suggest that the hydrophobic residues Phe192-Met193 could facilitate hydride transfer. 17beta-HSD1 appears to be unique among the members of the SDR protein family in that one of the two basic residues involved in the charge compensation of the 2'-phosphate does not belong to the Rossmann-fold motif. The remarkable stabilization of the NADP+ 2'-phosphate by the enzyme also clearly establishes its preference for this cofactor relative to NAD+. Analysis of the catalytic properties of, and estradiol binding to, the two mutants suggests that the His221-steroid O3 hydrogen bond plays an important role in substrate specificity.
| | The line below this paragraph, {{ABSTRACT_PUBMED_9525918}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 9525918 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_9525918}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Mutant]] | | [[Category: Mutant]] |
| [[Category: Nadp]] | | [[Category: Nadp]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 16:12:57 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 03:06:25 2008'' |
