1fdv
From Proteopedia
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==Overview== | ==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 ... | + | 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== | ||
| - | 1FDV is a | + | 1FDV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 and NAD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Estradiol_17-beta-dehydrogenase Estradiol 17-beta-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62] Structure known Active Site: CAT. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FDV OCA]. |
==Reference== | ==Reference== | ||
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[[Category: nad]] | [[Category: nad]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:28:51 2007'' |
Revision as of 12:23, 5 November 2007
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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 SO4 and NAD as ligands. Active as Estradiol 17-beta-dehydrogenase, with EC number 1.1.1.62 Structure known Active Site: CAT. 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 Mon Nov 5 14:28:51 2007
