1fdw

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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'''
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===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.
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(as it appears on PubMed at http://www.pubmed.gov), where 9525918 is the PubMed ID number.
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{{ABSTRACT_PUBMED_9525918}}
==About this Structure==
==About this Structure==
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[[Category: Mutant]]
[[Category: Mutant]]
[[Category: Nadp]]
[[Category: Nadp]]
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Revision as of 00:06, 1 July 2008

Image:1fdw.png

Template:STRUCTURE 1fdw

HUMAN 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE 1 MUTANT H221Q COMPLEXED WITH ESTRADIOL

Template:ABSTRACT PUBMED 9525918

About this Structure

1FDW is a Single protein structure of sequence from Homo sapiens. 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

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