Hydroxysteroid dehydrogenase

From Proteopedia

Contents 1 Function 2 Disease 3 Structural highlights 4 3D structures of hydroxysteroid dehydrogenase Function Hydroxysteroid dehydrogenase (HSD) catalyzes the dehydrogenation of hydroxysteroids. HSD is classified according to the number of the carbon it is acting on. 3-α HSD catalyzes the conversion of androsterone to 5α-androstane-3, 17-dione and 17-α estradiol to estrone. 3-α HSD (also named 17-α HSD) is a bile acid-metabolizing enzyme[1]. 7-α HSD is involved in the dehydrogenation of cholanate compounds and is a bile acid-inducible enzyme[2]. 20-α HSD is involved in the control of progesterone level in pregnancy of mice[3]. 11-β HSD converts 11-keto products like cortisone to cortisol[4]. 17-β HSD is involved in the conversion of androstenedione to testosterone[5]. See Human Keto Acyl Reductase. 3-β/17-β HSD catalyzes the reversible dehydrogenation of steroid compounds at position 3 and 17[6]. NAD and NADP are cofactors of HSD. Disease Deficiency of 17-β HSD caused by mutations are the cause of male hermaphroditism[7]. Deficiency of 3-β HSD caused by mutations are the cause of congenital adrenal hyperplasia[8]. Deficiency of 11-β HSD is associated with alcoholic and non-alcoholic chronic liver disease[9]. Structural highlights The structure of 3-α HSD is that of an α/β barrel with the cofactor NADP binding site at the C-terminal of the barrel[10]. Water molecules shown as red spheres. 3D structures of hydroxysteroid dehydrogenase Hydroxysteroid dehydrogenase 3D structures

Jmol._Canvas2D (Jmol) "jmolApplet1"[x] spinqualitylabelsall models Rat 3-α hydroxysteroid dehydrogenase dimer complex with cofactor NADP 1lwi Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

References

1. ↑ Rizner TL, Lin HK, Peehl DM, Steckelbroeck S, Bauman DR, Penning TM. Human type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2) and androgen metabolism in prostate cells. Endocrinology. 2003 Jul;144(7):2922-32. PMID:12810547 doi:http://dx.doi.org/10.1210/en.2002-0032
2. ↑ Haslewood ES, Haslewood GA. The specificity of a 7 alpha-hydroxy steroid dehydrogenase from Escherichia coli. Biochem J. 1976 Jul 1;157(1):207-10. PMID:786279
3. ↑ Hershkovitz L, Beuschlein F, Klammer S, Krup M, Weinstein Y. Adrenal 20alpha-hydroxysteroid dehydrogenase in the mouse catabolizes progesterone and 11-deoxycorticosterone and is restricted to the X-zone. Endocrinology. 2007 Mar;148(3):976-88. Epub 2006 Nov 22. PMID:17122075 doi:http://dx.doi.org/10.1210/en.2006-1100
4. ↑ Tomlinson JW, Walker EA, Bujalska IJ, Draper N, Lavery GG, Cooper MS, Hewison M, Stewart PM. 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocr Rev. 2004 Oct;25(5):831-66. PMID:15466942 doi:http://dx.doi.org/10.1210/er.2003-0031
5. ↑ Labrie F, Luu-The V, Lin SX, Labrie C, Simard J, Breton R, Belanger A. The key role of 17 beta-hydroxysteroid dehydrogenases in sex steroid biology. Steroids. 1997 Jan;62(1):148-58. PMID:9029730
6. ↑ de Launoit Y, Simard J, Durocher F, Labrie F. Androgenic 17 beta-hydroxysteroid dehydrogenase activity of expressed rat type I 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase. Endocrinology. 1992 Jan;130(1):553-5. PMID:1309351 doi:http://dx.doi.org/10.1210/endo.130.1.1309351
7. ↑ Boehmer AL, Brinkmann AO, Sandkuijl LA, Halley DJ, Niermeijer MF, Andersson S, de Jong FH, Kayserili H, de Vroede MA, Otten BJ, Rouwe CW, Mendonca BB, Rodrigues C, Bode HH, de Ruiter PE, Delemarre-van de Waal HA, Drop SL. 17Beta-hydroxysteroid dehydrogenase-3 deficiency: diagnosis, phenotypic variability, population genetics, and worldwide distribution of ancient and de novo mutations. J Clin Endocrinol Metab. 1999 Dec;84(12):4713-21. PMID:10599740 doi:http://dx.doi.org/10.1210/jcem.84.12.6174
8. ↑ Moisan AM, Ricketts ML, Tardy V, Desrochers M, Mebarki F, Chaussain JL, Cabrol S, Raux-Demay MC, Forest MG, Sippell WG, Peter M, Morel Y, Simard J. New insight into the molecular basis of 3beta-hydroxysteroid dehydrogenase deficiency: identification of eight mutations in the HSD3B2 gene eleven patients from seven new families and comparison of the functional properties of twenty-five mutant enzymes. J Clin Endocrinol Metab. 1999 Dec;84(12):4410-25. PMID:10599696
9. ↑ Stewart PM, Burra P, Shackleton CH, Sheppard MC, Elias E. 11 beta-Hydroxysteroid dehydrogenase deficiency and glucocorticoid status in patients with alcoholic and non-alcoholic chronic liver disease. J Clin Endocrinol Metab. 1993 Mar;76(3):748-51. PMID:8445034 doi:http://dx.doi.org/10.1210/jcem.76.3.8445034
10. ↑ Bennett MJ, Schlegel BP, Jez JM, Penning TM, Lewis M. Structure of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase complexed with NADP+. Biochemistry. 1996 Aug 20;35(33):10702-11. PMID:8718859 doi:10.1021/bi9604688