1fdv

From Proteopedia

Revision as of 14:45, 12 November 2007

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

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