Showing papers on "Hydroxysteroid dehydrogenase published in 2016"
TL;DR: The data indicated that OsHSD1 plays a specialized role in cuticle formation and lipid homeostasis, probably by mediating sterol signaling, and provides new insights into oil-body associated proteins involved in wax and lipid metabolism.
24 citations
TL;DR: The crystal structure of 7β‐hydroxysteroid dehydrogenase from Collinsella aerofaciens reveals a loop gating active‐site accessibility, the bases of the specificity for NADP+, and the general architecture of the steroid binding site.
Abstract: Hydroxysteroid dehydrogenases are of great interest as biocatalysts for transformations involving steroid substrates. They feature a high degree of stereo- and regio-selectivity, acting on a defined atom with a specific configuration of the steroid nucleus. The crystal structure of 7β-hydroxysteroid dehydrogenase from Collinsella aerofaciens reveals a loop gating active-site accessibility, the bases of the specificity for NADP(+) , and the general architecture of the steroid binding site. Comparison with 7α-hydroxysteroid dehydrogenase provides a rationale for the opposite stereoselectivity. The presence of a C-terminal extension reshapes the substrate site of the β-selective enzyme, possibly leading to an inverted orientation of the bound substrate. Proteins 2016; 84:859-865. © 2016 Wiley Periodicals, Inc.
23 citations
TL;DR: DHRS11 represents a novel type of 17β-hydroxysteroid dehydrogenase with unique catalytic properties and tissue distribution and was observed widely in human tissues, most abundantly in testis, small intestine, colon, kidney and cancer cell lines.
22 citations
TL;DR: The 3-hydroxy-13β-D-secooxime has an IC50 value of 0.070 μM and is one of the most effective 17β-HSD1 inhibitors reported to date in the literature, i.e. more efficient inhibition in the presence of NADH than NADPH.
Abstract: The inhibitory effects of 13-epimeric estrones, D-secooxime and D-secoalcohol estrone compounds on human placental 17β-hydroxysteroid dehydrogenase type 1 isozyme (17β-HSD1) were investigated. The transformation of estrone to 17β-estradiol was studied by an in vitro radiosubstrate incubation method. 13α-Estrone inhibited the enzyme activity effectively with an IC50 value of 1.2 μM, which indicates that enzyme affinity is similar to that of the natural estrone substrate. The 13β derivatives and the compounds bearing a 3-hydroxy group generally exerted stronger inhibition than the 13α and 3-ether counterparts. The 3-hydroxy-13β-D-secoalcohol and the 3-hydroxy-13α-D-secooxime displayed an outstanding cofactor dependence, i.e. more efficient inhibition in the presence of NADH than NADPH. The 3-hydroxy-13β-D-secooxime has an IC50 value of 0.070 μM and is one of the most effective 17β-HSD1 inhibitors reported to date in the literature.
14 citations
TL;DR: Novel compound heterozygous mutations in HSD17B3, composed of the nonsense mutation C206X and the missense mutation G133R, are reported in three Tunisian patients from two non-consanguineous families, indicating an essential role of G133 in the arrangement of the cofactor binding pocket, thus explaining the loss-of-function of 17β-HSD3 mutant G 133R.
14 citations
TL;DR: The chemical synthesis of four stereoisomers of 16β-(m-carbamoylbenzyl)-estradiol, a potent reversible inhibitor of 17β-hydroxysteroid dehydrogenase type 1, and two intermediates was performed, and no compound showed an androgenic activity.
12 citations
TL;DR: The first fluorescent inhibitor of this enzyme is designed and synthesized by combining a fluorogenic dansyl moiety to the chemical structure of a known inhibitor of 17β-HSD3.
11 citations
TL;DR: The crystal structure of 17β-HSD14, a SDR enzyme able to oxidize estradiol and 5-androstenediol using NAD(+), is determined as the holo form and as ternary complexes with estrone and with the first potent, nonsteroidal inhibitor.
Abstract: 17β-HSD14 is a SDR enzyme able to oxidize estradiol and 5-androstenediol using NAD+. We determined the crystal structure of this human enzyme as the holo form and as ternary complexes with estrone and with the first potent, nonsteroidal inhibitor. The structures reveal a conical, rather large and lipophilic binding site and are the starting point for structure-based inhibitor design. The two natural variants (S205 and T205) were characterized and adopt a similar structure.
11 citations
TL;DR: Four different classes of new 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2) inhibitors were synthesized, in order to lower the cytotoxicity exhibited by the lead compound A, via disrupting the linearity and the aromaticity of the biphenyl moiety.
6 citations
TL;DR: Several different dehydroepiandrosterone derivatives could have therapeutic potential for the treatment of prostate cancer and benign prostatic hyperplasia and inhibition of 17β-HSD5 by these compounds was studied.
Abstract: The enzyme type 5 17β-hydroxysteroid dehydrogenase 5 (17β-HSD5) catalyzes the transformation of androstenedione (4-dione) to testosterone (T) in the prostate. This metabolic pathway remains active in cancer patients receiving androgen deprivation therapy. Since physicians seek to develop advantageous and better new treatments to increase the average survival of these patients, we synthesized several different dehydroepiandrosterone derivatives. These compounds have a pyrazole or imidazole function at C-17 and an ester moiety at C-3 and were studied as inhibitors of 17β-HSD5. The kinetic parameters of this enzyme were determined for use in inhibition assays. Their pharmacological effect was also determined on gonadectomized hamsters treated with Δ4-androstenedione (4-dione) or testosterone (T) and/or the novel compounds. The results indicated that the incorporation of a heterocycle at C-17 induced strong 17β-HSD5 inhibition. These derivatives decreased flank organ diameter and prostate weight in ca...
4 citations