1qyw

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Revision as of 16:51, 12 November 2007

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spinqualitylabelsall models 1qyw, resolution 1.63Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of human estrogenic 17beta-hydroxysteroid dehydrogenase comlex with androstanedione and NADP

Overview

Human estrogenic 17beta-hydroxysteroid dehydrogenase (17beta-HSD1), a, member of the short chain dehydrogenase/reductase (SDR) family, is, responsible for the biosynthesis of all active estrogens. The crystal, structures of two C19-steroid ternary complexes, (17beta-HSD1-androstanedione-NADP and 17beta-HSD1-androstenedione-NADP), reveal the critical role of Leu149 in regulating the substrate specificity, and provide novel insight into the different fates of a conserved, glutamate residue in the estrogen-specific proteins upon the binding of, the keto and hydroxyl groups of steroids. The whole NADP molecule can be, unambiguously defined in the NADP binary complex, whereas both ternary, complexes show that the nicotinamide moiety of NADP cannot be located in, the density maps. In both ternary complexes, the expected position of, carboxamide oxygen of NADP is occupied by a water molecule, which makes a, bifurcated hydrogen bond with the O3 of C19-steroid and the main chain, nitrogen of Val188. These results demonstrate that the hydrogen bonding, interaction between the main chain amide group and the carboxamide group, of NAD(P)(H) plays an important role in anchoring the nicotinamide ring to, the enzyme. This finding is substantiated by structural analyses of all 33, NAD(P)(H) complexes of different SDR proteins, because 29 structures of 33, show this interaction. This common feature reveals a general mechanism, among the SDR family, providing a rational basis for inhibitor design, against biologically relevant SDR targets.

About this Structure

1QYW is a Single protein structure of sequence from Homo sapiens with 5SD, NAP and GOL as ligands. Active as Estradiol 17-beta-dehydrogenase, with EC number 1.1.1.62 Full crystallographic information is available from OCA.

Reference

Cofactor hydrogen bonding onto the protein main chain is conserved in the short chain dehydrogenase/reductase family and contributes to nicotinamide orientation., Shi R, Lin SX, J Biol Chem. 2004 Apr 16;279(16):16778-85. Epub 2004 Feb 13. PMID:14966133

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