1fdv
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Type 1 17beta-hydroxysteroid dehydrogenase (17beta-HSD1), a member of the | + | 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. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Breton, R.]] | [[Category: Breton, R.]] | ||
| - | [[Category: Fontecilla-Camps, J | + | [[Category: Fontecilla-Camps, J C.]] |
[[Category: Housset, D.]] | [[Category: Housset, D.]] | ||
[[Category: Mazza, C.]] | [[Category: Mazza, C.]] | ||
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[[Category: nad]] | [[Category: nad]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:37:39 2008'' |
Revision as of 10:37, 21 February 2008
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HUMAN 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE 1 MUTANT H221L COMPLEXED WITH NAD+
Overview
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.
About this Structure
1FDV is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Estradiol 17-beta-dehydrogenase, with EC number 1.1.1.62 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Unusual charge stabilization of NADP+ in 17beta-hydroxysteroid dehydrogenase., Mazza C, Breton R, Housset D, Fontecilla-Camps JC, J Biol Chem. 1998 Apr 3;273(14):8145-52. PMID:9525918
Page seeded by OCA on Thu Feb 21 12:37:39 2008
