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Luu-The, V., Labrie, C., Zhao, H.F., Couet, J., Lachance, Y., Simard, J., Leblanc, G., Coté, J., Bérubé, D. and Gagné, R. (1989) Characterization of cDNAs for Human Estradiol 17beta-Dehydrogenase and Assignment of the Gene to Chromosome 17: Evidence of Two mRNA Species with Distinct 5'-Termini in Human Placenta. Molecular Endocrinology, 3, 1301-1309.
https://doi.org/10.1210/mend-3-8-1301

has been cited by the following article:

• TITLE: Crystal Structures of Human 17β-Hydroxysteroid Dehydrogenase Type 1 Complexed with the Dual-Site Inhibitor EM-139

  AUTHORS: Tang Li, Daowei Zhu, Fernand Labrie, Shengxiang Lin

  KEYWORDS: 17β-HSD1, Inhibitor, Complex Structure, Estrogen-Dependent Diseases

  JOURNAL NAME: Health, Vol.10 No.8, August 16, 2018

  ABSTRACT: Human 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) catalyzes the biosynthesis of the most potent natural estrogen 17β-estradiol (E2) from estrone (E1) in the ovary and peripheral tissues, playing a pivotal role in the progression of estrogen-dependent diseases. N-n-Butyl-N-methyl-ll-(16'α-chloro-3',17'β-dihydroxyestra-1',3',5'(10')-trien-7'α-yl)undecanamide (EM-139) was previously described as a dual-site inhibitor that can inhibit 17β-HSD1 transforming E1 into E2 and also inhibit estrogen receptor. In the present report, we describe the co-crystallization of EM-139 with 17β-HSD1 as well as the analysis of the three-dimensional structure of the enzyme/inhibitor complex. The crystal is grown under similar condition as native crystals, whereas the space group is changed to I121 never observed in other 17β-HSD1 crystals before. The steroidal moiety of the bound EM-139 molecule has shown a binding pattern similar to E2 in the E2 binary complex. The O-3 of the inhibitor develops hydrogen bonds with residues His221 and Glu282, whereas the O-17 makes hydrogen bonds with Ser142 and Tyr155. The bulky 7α-alkyl moiety of the inhibitor, which is essential for its anti-estrogenic activity but cannot be defined in the electron density, may compromise the inhibitory effect of EM-139 to 17β-HSD1. Moreover, the 16α-Cl atom shows no obvious interaction with surrounding residues. The atomic level understanding of the inhibitory mechanism of EM-139 provides important information for the inhibitor design of 17β-HSD1, which will facilitate future development of more potent and selective inhibitors of the enzyme for therapeutic purposes.