Crystallographic Studies of Steroid-Protein Interactions

  • Arthur F. MonzingoEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1135)


Steroid molecules have a wide range of function in eukaryotes, including the control and maintenance of membranes, hormonal control of transcription, and intracellular signaling. X-ray crystallography has served as a successful tool for gaining understanding of the structural and mechanistic aspects of these functions by providing snapshots of steroids in complex with various types of proteins. These proteins include nuclear receptors activated by steroid hormones, several families of enzymes involved in steroid synthesis and metabolism, and proteins involved in signaling and trafficking pathways. Proteins found in some bacteria that bind and metabolize steroids have been investigated as well. A survey of the steroid-protein complexes that have been studied using crystallography and the insight learned from them is presented.


Protein-steroid complex Ligand binding pocket Protein structure Nuclear receptor Steroid metabolism Steroid trafficking 


  1. 1.
    Ourisson G, Nakatani Y. The terpenoid theory of the origin of cellular life: the evolution of terpenoids to cholesterol. Chem Biol. 1994;1:11–23.CrossRefPubMedGoogle Scholar
  2. 2.
    Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, et al. The protein data bank. Nucleic Acids Res. 2000;28:235–42.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Lamb DC, Lei L, Warrilow AG, Lepesheva GI, Mullins JG, Waterman MR, et al. The first virally encoded cytochrome p450. J Virol. 2009;83:8266–9.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Strushkevich N, MacKenzie F, Cherkesova T, Grabovec I, Usanov S, Park HW. Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system. Proc Natl Acad Sci U S A. 2011;108:10139–43.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Pikuleva IA. Cholesterol-metabolizing cytochromes P450. Drug Metab Dispos. 2006;34:513–20.CrossRefPubMedGoogle Scholar
  6. 6.
    Simpson ER, Boyd GS. The cholesterol side-chain cleavage system of bovine adrenal cortex. Eur J Biochem. 1967;2:275–85.CrossRefPubMedGoogle Scholar
  7. 7.
    Burstein S, Middleditch BS, Gut M. Mass spectrometric study of the enzymatic conversion of cholesterol to (22R)-22-hydroxycholesterol, (20R,22R)-20,22-dihydroxycholesterol, and pregnenolone, and of (22R)-22-hydroxycholesterol to the lgycol and pregnenolone in bovine adrenocortical preparations. Mode of oxygen incorporation. J Biol Chem. 1975;250:9028–37.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Lambeth JD, Kitchen SE, Farooqui AA, Tuckey R, Kamin H. Cytochrome P-450scc-substrate interactions. Studies of binding and catalytic activity using hydroxycholesterols. J Biol Chem. 1982;257:1876–84.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Mast N, Annalora AJ, Lodowski DT, Palczewski K, Stout CD, Pikuleva IA. Structural basis for three-step sequential catalysis by the cholesterol side chain cleavage enzyme CYP11A1. J Biol Chem. 2011;286:5607–13.CrossRefPubMedGoogle Scholar
  10. 10.
    Tomaschitz A, Pilz S, Ritz E, Obermayer-Pietsch B, Pieber TR. Aldosterone and arterial hypertension. Nat Rev Endocrinol. 2010;6:83–93.CrossRefPubMedGoogle Scholar
  11. 11.
    Strushkevich N, Gilep AA, Shen L, Arrowsmith CH, Edwards AM, Usanov SA, et al. Structural insights into aldosterone synthase substrate specificity and targeted inhibition. Mol Endocrinol. 2013;27:315–24.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev. 2011;32:81–151.CrossRefPubMedGoogle Scholar
  13. 13.
    Yap TA, Carden CP, Attard G, de Bono JS. Targeting CYP17: established and novel approaches in prostate cancer. Curr Opin Pharmacol. 2008;8:449–57.CrossRefPubMedGoogle Scholar
  14. 14.
    DeVore NM, Scott EE. Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001. Nature. 2012;482:116–9.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Björkhem I, Meaney S. Brain cholesterol: long secret life behind a barrier. Arterioscler Thromb Vasc Biol. 2004;24:806–15.CrossRefPubMedGoogle Scholar
  16. 16.
    Björkhem I. Crossing the barrier: oxysterols as cholesterol transporters and metabolic modulators in the brain. J Intern Med. 2006;260:493–508.CrossRefPubMedGoogle Scholar
  17. 17.
    Mast N, White MA, Bjorkhem I, Johnson EF, Stout CD, Pikuleva IA. Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain. Proc Natl Acad Sci U S A. 2008;105:9546–51.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Aoyama Y, Noshiro M, Gotoh O, Imaoka S, Funae Y, Kurosawa N, et al. Sterol 14-demethylase P450 (P45014DM*) is one of the most ancient and conserved P450 species. J Biochem. 1996;119:926–33.CrossRefPubMedGoogle Scholar
  19. 19.
    Monk BC, Tomasiak TM, Keniya MV, Huschmann FU, Tyndall JD, O’Connell JD, et al. Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer. Proc Natl Acad Sci U S A. 2014;111:3865–70.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Beh CT, Rine J. A role for yeast oxysterol-binding protein homologs in endocytosis and in the maintenance of intracellular sterol-lipid distribution. J Cell Sci. 2004;117:2983–96.CrossRefPubMedGoogle Scholar
  21. 21.
    Wang PY, Weng J, Anderson RG. OSBP is a cholesterol-regulated scaffolding protein in control of ERK 1/2 activation. Science. 2005;307:1472–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Im YJ, Raychaudhuri S, Prinz WA, Hurley JH. Structural mechanism for sterol sensing and transport by OSBP-related proteins. Nature. 2005;437:154–8.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Koag MC, Cheun Y, Kou Y, Ouzon-Shubeita H, Min K, Monzingo AF, et al. Synthesis and structure of 16,22-diketocholesterol bound to oxysterol-binding protein Osh4. Steroids. 2013;78:938–44.CrossRefPubMedGoogle Scholar
  24. 24.
    Pentchev PG. Niemann-Pick C research from mouse to gene. Biochim Biophys Acta. 2004;1685:3–7.CrossRefPubMedGoogle Scholar
  25. 25.
    Xu S, Benoff B, Liou HL, Lobel P, Stock AM. Structural basis of sterol binding by NPC2, a lysosomal protein deficient in Niemann-Pick type C2 disease. J Biol Chem. 2007;282:23525–31.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Friedland N, Liou HL, Lobel P, Stock AM. Structure of a cholesterol-binding protein deficient in Niemann-Pick type C2 disease. Proc Natl Acad Sci U S A. 2003;100:2512–7.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Kwon HJ, Abi-Mosleh L, Wang ML, Deisenhofer J, Goldstein JL, Brown MS, et al. Structure of N-terminal domain of NPC1 reveals distinct subdomains for binding and transfer of cholesterol. Cell. 2009;137:1213–24.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Li X, Wang J, Coutavas E, Shi H, Hao Q, Blobel G. Structure of human Niemann-Pick C1 protein. Proc Natl Acad Sci U S A. 2016;113:8212–7.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Gong X, Qian H, Zhou X, Wu J, Wan T, Cao P, et al. Structural insights into the Niemann-Pick C1 (NPC1)-mediated cholesterol transfer and Ebola infection. Cell. 2016;165:1467–78.CrossRefPubMedGoogle Scholar
  30. 30.
    Li X, Saha P, Li J, Blobel G, Pfeffer SR. Clues to the mechanism of cholesterol transfer from the structure of NPC1 middle lumenal domain bound to NPC2. Proc Natl Acad Sci U S A. 2016;113:10079–84.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Huang P, Nedelcu D, Watanabe M, Jao C, Kim Y, Liu J, et al. Cellular cholesterol directly activates smoothened in hedgehog signaling. Cell. 2016;166:1176–87.e14.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Busillo JM, Rhen T, Cidlowski JA. Steroid hormone action. In: Strauss JF, editor. Yen and Jaffe’s reproductive endocrinology. 7th ed. Philadelphia, PA: Elsevier; 2014. p. 93–107.CrossRefGoogle Scholar
  33. 33.
    Dawson NL, Lewis TE, Das S, Lees JG, Lee D, Ashford P, et al. CATH: an expanded resource to predict protein function through structure and sequence. Nucleic Acids Res. 2017;45:D289–D95.CrossRefPubMedGoogle Scholar
  34. 34.
    Beato M, Sánchez-Pacheco A. Interaction of steroid hormone receptors with the transcription initiation complex. Endocr Rev. 1996;17:587–609.CrossRefPubMedGoogle Scholar
  35. 35.
    Tanenbaum DM, Wang Y, Williams SP, Sigler PB. Crystallographic comparison of the estrogen and progesterone receptor’s ligand binding domains. Proc Natl Acad Sci U S A. 1998;95:5998–6003.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Veldscholte J, Voorhorst-Ogink MM, Bolt-de Vries J, van Rooij HC, Trapman J, Mulder E. Unusual specificity of the androgen receptor in the human prostate tumor cell line LNCaP: high affinity for progestagenic and estrogenic steroids. Biochim Biophys Acta. 1990;1052:187–94.CrossRefPubMedGoogle Scholar
  37. 37.
    Thornton JW. Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions. Proc Natl Acad Sci U S A. 2001;98:5671–6.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Seckl JR. 11beta-hydroxysteroid dehydrogenases: changing glucocorticoid action. Curr Opin Pharmacol. 2004;4:597–602.CrossRefPubMedGoogle Scholar
  39. 39.
    Tsai MJ, O’Malley BW. Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu Rev Biochem. 1994;63:451–86.CrossRefPubMedGoogle Scholar
  40. 40.
    Brzozowski AM, Pike AC, Dauter Z, Hubbard RE, Bonn T, Engström O, et al. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature. 1997;389:753–8.CrossRefPubMedGoogle Scholar
  41. 41.
    Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA, et al. The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell. 1998;95:927–37.CrossRefPubMedGoogle Scholar
  42. 42.
    Williams SP, Sigler PB. Atomic structure of progesterone complexed with its receptor. Nature. 1998;393:392–6.CrossRefPubMedGoogle Scholar
  43. 43.
    Matias PM, Donner P, Coelho R, Thomaz M, Peixoto C, Macedo S, et al. Structural evidence for ligand specificity in the binding domain of the human androgen receptor. Implications for pathogenic gene mutations. J Biol Chem. 2000;275:26164–71.CrossRefPubMedGoogle Scholar
  44. 44.
    Pereira de Jésus-Tran K, Côté PL, Cantin L, Blanchet J, Labrie F, Breton R. Comparison of crystal structures of human androgen receptor ligand-binding domain complexed with various agonists reveals molecular determinants responsible for binding affinity. Protein Sci. 2006;15:987–99.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Sack JS, Kish KF, Wang C, Attar RM, Kiefer SE, An Y, et al. Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone. Proc Natl Acad Sci U S A. 2001;98:4904–9.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Reichardt HM, Tronche F, Berger S, Kellendonk C, Schütz G. New insights into glucocorticoid and mineralocorticoid signaling: lessons from gene targeting. Adv Pharmacol. 2000;47:1–21.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD, et al. Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell. 2002;110:93–105.CrossRefPubMedGoogle Scholar
  48. 48.
    He Y, Yi W, Suino-Powell K, Zhou XE, Tolbert WD, Tang X, et al. Structures and mechanism for the design of highly potent glucocorticoids. Cell Res. 2014;24:713–26.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Funder JW. Glucocorticoid and mineralocorticoid receptors: biology and clinical relevance. Annu Rev Med. 1997;48:231–40.CrossRefPubMedGoogle Scholar
  50. 50.
    Li Y, Suino K, Daugherty J, Xu HE. Structural and biochemical mechanisms for the specificity of hormone binding and coactivator assembly by mineralocorticoid receptor. Mol Cell. 2005;19:367–80.CrossRefPubMedGoogle Scholar
  51. 51.
    Fagart J, Huyet J, Pinon GM, Rochel M, Mayer C, Rafestin-Oblin ME. Crystal structure of a mutant mineralocorticoid receptor responsible for hypertension. Nat Struct Mol Biol. 2005;12:554–5.CrossRefPubMedGoogle Scholar
  52. 52.
    Kallen JA, Schlaeppi JM, Bitsch F, Geisse S, Geiser M, Delhon I, et al. X-ray structure of the hRORalpha LBD at 1.63 A: structural and functional data that cholesterol or a cholesterol derivative is the natural ligand of RORalpha. Structure. 2002;10:1697–707.CrossRefPubMedGoogle Scholar
  53. 53.
    Kallen J, Schlaeppi JM, Bitsch F, Delhon I, Fournier B. Crystal structure of the human RORalpha ligand binding domain in complex with cholesterol sulfate at 2.2 A. J Biol Chem. 2004;279:14033–8.CrossRefPubMedGoogle Scholar
  54. 54.
    Jin L, Martynowski D, Zheng S, Wada T, Xie W, Li Y. Structural basis for hydroxycholesterols as natural ligands of orphan nuclear receptor RORgamma. Mol Endocrinol. 2010;24:923–9.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, Kliewer SA. The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest. 1998;102:1016–23.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Delfosse V, Dendele B, Huet T, Grimaldi M, Boulahtouf A, Gerbal-Chaloin S, et al. Synergistic activation of human pregnane X receptor by binary cocktails of pharmaceutical and environmental compounds. Nat Commun. 2015;6:8089.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Penning TM, Drury JE. Human aldo-keto reductases: function, gene regulation, and single nucleotide polymorphisms. Arch Biochem Biophys. 2007;464:241–50.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Rizner TL, Smuc T, Rupreht R, Sinkovec J, Penning TM. AKR1C1 and AKR1C3 may determine progesterone and estrogen ratios in endometrial cancer. Mol Cell Endocrinol. 2006;248:126–35.CrossRefPubMedGoogle Scholar
  59. 59.
    Steckelbroeck S, Jin Y, Gopishetty S, Oyesanmi B, Penning TM. Human cytosolic 3alpha-hydroxysteroid dehydrogenases of the aldo-keto reductase superfamily display significant 3beta-hydroxysteroid dehydrogenase activity: implications for steroid hormone metabolism and action. J Biol Chem. 2004;279:10784–95.CrossRefPubMedGoogle Scholar
  60. 60.
    Couture JF, Legrand P, Cantin L, Luu-The V, Labrie F, Breton R. Human 20alpha-hydroxysteroid dehydrogenase: crystallographic and site-directed mutagenesis studies lead to the identification of an alternative binding site for C21-steroids. J Mol Biol. 2003;331:593–604.CrossRefPubMedGoogle Scholar
  61. 61.
    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;144:2922–32.CrossRefPubMedGoogle Scholar
  62. 62.
    Zhang B, Hu XJ, Wang XQ, Thériault JF, Zhu DW, Shang P, et al. Human 3α-hydroxysteroid dehydrogenase type 3: structural clues of 5α-DHT reverse binding and enzyme down-regulation decreasing MCF7 cell growth. Biochem J. 2016;473:1037–46.CrossRefPubMedGoogle Scholar
  63. 63.
    Nahoum V, Gangloff A, Legrand P, Zhu DW, Cantin L, Zhorov BS, et al. Structure of the human 3alpha-hydroxysteroid dehydrogenase type 3 in complex with testosterone and NADP at 1.25-A resolution. J Biol Chem. 2001;276:42091–8.CrossRefPubMedGoogle Scholar
  64. 64.
    Zhang B, Zhu DW, Hu XJ, Zhou M, Shang P, Lin SX. Human 3-alpha hydroxysteroid dehydrogenase type 3 (3α-HSD3): the V54L mutation restricting the steroid alternative binding and enhancing the 20α-HSD activity. J Steroid Biochem Mol Biol. 2014;141:135–43.CrossRefPubMedGoogle Scholar
  65. 65.
    Qiu W, Zhou M, Labrie F, Lin SX. Crystal structures of the multispecific 17beta-hydroxysteroid dehydrogenase type 5: critical androgen regulation in human peripheral tissues. Mol Endocrinol. 2004;18:1798–807.CrossRefPubMedGoogle Scholar
  66. 66.
    Bennett MJ, Albert RH, Jez JM, Ma H, Penning TM, Lewis M. Steroid recognition and regulation of hormone action: crystal structure of testosterone and NADP+ bound to 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase. Structure. 1997;5:799–812.CrossRefPubMedGoogle Scholar
  67. 67.
    Couture JF, Legrand P, Cantin L, Labrie F, Luu-The V, Breton R. Loop relaxation, a mechanism that explains the reduced specificity of rabbit 20alpha-hydroxysteroid dehydrogenase, a member of the aldo-keto reductase superfamily. J Mol Biol. 2004;339:89–102.CrossRefPubMedGoogle Scholar
  68. 68.
    Faucher F, Cantin L, Pereira de Jésus-Tran K, Lemieux M, Luu-The V, Labrie F, et al. Mouse 17alpha-hydroxysteroid dehydrogenase (AKR1C21) binds steroids differently from other aldo-keto reductases: identification and characterization of amino acid residues critical for substrate binding. J Mol Biol. 2007;369:525–40.CrossRefPubMedGoogle Scholar
  69. 69.
    Di Costanzo L, Drury JE, Penning TM, Christianson DW. Crystal structure of human liver Delta4-3-ketosteroid 5beta-reductase (AKR1D1) and implications for substrate binding and catalysis. J Biol Chem. 2008;283:16830–9.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Faucher F, Cantin L, Luu-The V, Labrie F, Breton R. Crystal structures of human Delta4-3-ketosteroid 5beta-reductase (AKR1D1) reveal the presence of an alternative binding site responsible for substrate inhibition. Biochemistry. 2008;47:13537–46.CrossRefPubMedGoogle Scholar
  71. 71.
    Chen M, Drury JE, Christianson DW, Penning TM. Conversion of human steroid 5β-reductase (AKR1D1) into 3β-hydroxysteroid dehydrogenase by single point mutation E120H: example of perfect enzyme engineering. J Biol Chem. 2012;287:16609–22.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Oppermann U, Filling C, Hult M, Shafqat N, Wu X, Lindh M, et al. Short-chain dehydrogenases/reductases (SDR): the 2002 update. Chem Biol Interact. 2003;143-144:247–53.CrossRefPubMedGoogle Scholar
  73. 73.
    Kavanagh KL, Jörnvall H, Persson B, Oppermann U. Medium- and short-chain dehydrogenase/reductase gene and protein families: the SDR superfamily: functional and structural diversity within a family of metabolic and regulatory enzymes. Cell Mol Life Sci. 2008;65:3895–906.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Miyoshi Y, Ando A, Shiba E, Taguchi T, Tamaki Y, Noguchi S. Involvement of up-regulation of 17beta-hydroxysteroid dehydrogenase type 1 in maintenance of intratumoral high estradiol levels in postmenopausal breast cancers. Int J Cancer. 2001;94:685–9.CrossRefPubMedGoogle Scholar
  75. 75.
    Azzi A, Rehse PH, Zhu DW, Campbell RL, Labrie F, Lin SX. Crystal structure of human estrogenic 17 beta-hydroxysteroid dehydrogenase complexed with 17 beta-estradiol. Nat Struct Biol. 1996;3:665–8.CrossRefPubMedGoogle Scholar
  76. 76.
    Breton R, Housset D, Mazza C, Fontecilla-Camps JC. The structure of a complex of human 17beta-hydroxysteroid dehydrogenase with estradiol and NADP+ identifies two principal targets for the design of inhibitors. Structure. 1996;4:905–15.CrossRefPubMedGoogle Scholar
  77. 77.
    Mazza C, Breton R, Housset D, Fontecilla-Camps JC. Unusual charge stabilization of NADP+ in 17beta-hydroxysteroid dehydrogenase. J Biol Chem. 1998;273:8145–52.CrossRefPubMedGoogle Scholar
  78. 78.
    Han Q, Campbell RL, Gangloff A, Huang YW, Lin SX. Dehydroepiandrosterone and dihydrotestosterone recognition by human estrogenic 17beta-hydroxysteroid dehydrogenase. C-18/c-19 steroid discrimination and enzyme-induced strain. J Biol Chem. 2000;275:1105–11.CrossRefPubMedGoogle Scholar
  79. 79.
    Shi R, Lin SX. Cofactor hydrogen bonding onto the protein main chain is conserved in the short chain dehydrogenase/reductase family and contributes to nicotinamide orientation. J Biol Chem. 2004;279:16778–85.CrossRefPubMedGoogle Scholar
  80. 80.
    Stewart PM, Krozowski ZS. 11 beta-hydroxysteroid dehydrogenase. Vitam Horm. 1999;57:249–324.CrossRefPubMedGoogle Scholar
  81. 81.
    Zhang J, Osslund TD, Plant MH, Clogston CL, Nybo RE, Xiong F, et al. Crystal structure of murine 11 beta-hydroxysteroid dehydrogenase 1: an important therapeutic target for diabetes. Biochemistry. 2005;44:6948–57.CrossRefPubMedGoogle Scholar
  82. 82.
    Brennan PJ, Nikaido H. The envelope of mycobacteria. Annu Rev Biochem. 1995;64:29–63.CrossRefPubMedGoogle Scholar
  83. 83.
    Bernhardt R. Cytochromes P450 as versatile biocatalysts. J Biotechnol. 2006;124:128–45.CrossRefPubMedGoogle Scholar
  84. 84.
    Podust LM, Yermalitskaya LV, Lepesheva GI, Podust VN, Dalmasso EA, Waterman MR. Estriol bound and ligand-free structures of sterol 14alpha-demethylase. Structure. 2004;12:1937–45.CrossRefPubMedGoogle Scholar
  85. 85.
    Cupp-Vickery J, Anderson R, Hatziris Z. Crystal structures of ligand complexes of P450eryF exhibiting homotropic cooperativity. Proc Natl Acad Sci U S A. 2000;97:3050–5.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Herzog K, Bracco P, Onoda A, Hayashi T, Hoffmann K, Schallmey A. Enzyme-substrate complex structures of CYP154C5 shed light on its mode of highly selective steroid hydroxylation. Acta Crystallogr D Biol Crystallogr. 2014;70:2875–89.CrossRefPubMedGoogle Scholar
  87. 87.
    Jóźwik IK, Kiss FM, Gricman Ł, Abdulmughni A, Brill E, Zapp J, et al. Structural basis of steroid binding and oxidation by the cytochrome P450 CYP109E1 from Bacillus megaterium. FEBS J. 2016;283:4128–48.CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Edwards CA, Orr JC. Comparison of the 3alpha-and 20beta-hydroxysteroid dehydrogenase activities of the cortisone reductase of Streptomyces hydrogenans. Biochemistry. 1978;17:4370–6.CrossRefPubMedGoogle Scholar
  89. 89.
    Ghosh D, Erman M, Wawrzak Z, Duax WL, Pangborn W. Mechanism of inhibition of 3 alpha, 20 beta-hydroxysteroid dehydrogenase by a licorice-derived steroidal inhibitor. Structure. 1994;2:973–80.CrossRefPubMedGoogle Scholar
  90. 90.
    Benach J, Filling C, Oppermann UC, Roversi P, Bricogne G, Berndt KD, et al. Structure of bacterial 3beta/17beta-hydroxysteroid dehydrogenase at 1.2 A resolution: a model for multiple steroid recognition. Biochemistry. 2002;41:14659–68.CrossRefPubMedGoogle Scholar
  91. 91.
    Knol J, Bodewits K, Hessels GI, Dijkhuizen L, van der Geize R. 3-Keto-5alpha-steroid Delta(1)-dehydrogenase from Rhodococcus erythropolis SQ1 and its orthologue in Mycobacterium tuberculosis H37Rv are highly specific enzymes that function in cholesterol catabolism. Biochem J. 2008;410:339–46.CrossRefPubMedGoogle Scholar
  92. 92.
    Rohman A, van Oosterwijk N, Thunnissen AM, Dijkstra BW. Crystal structure and site-directed mutagenesis of 3-ketosteroid Δ1-dehydrogenase from Rhodococcus erythropolis SQ1 explain its catalytic mechanism. J Biol Chem. 2013;288:35559–68.CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    van Oosterwijk N, Knol J, Dijkhuizen L, van der Geize R, Dijkstra BW. Structure and catalytic mechanism of 3-ketosteroid-Delta4-(5α)-dehydrogenase from Rhodococcus jostii RHA1 genome. J Biol Chem. 2012;287:30975–83.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Li J, Vrielink A, Brick P, Blow DM. Crystal structure of cholesterol oxidase complexed with a steroid substrate: implications for flavin adenine dinucleotide dependent alcohol oxidases. Biochemistry. 1993;32:11507–15.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Center for Biomedical Research SupportUniversity of Texas at AustinAustinUSA

Personalised recommendations