1gs4 › Citations

Structural basis for the glucocorticoid response in a mutant human androgen receptor (AR(ccr)) derived from an androgen-independent prostate cancer.

Matias PM, Carrondo MA, Coelho R, Thomaz M, Zhao XY, Wegg A, Crusius K, Egner U, Donner P
J Med Chem 45 1439-46 (2002)
Cited: 55 times
EuropePMC logo PMID: 11906285

Abstract

The crystal structure of a mutant androgen receptor (AR) ligand-binding domain (LBD) in complex with the agonist 9alpha-fluorocortisol has been determined at 1.95 A resolution. This mutant AR contains two mutations (L701H and T877A) and was previously reported as a high-affinity cortisol/cortisone responsive AR (AR(ccr)) isolated from the androgen-independent human prostate cancer cell lines MDA PCa 2a and 2b (Zhao et al. Nature Med. 2000, 6, 703-6). The three-dimensional structure of the AR(ccr) LBD complexed with 9alpha-fluorocortisol shows the typical conformation of an agonist-bound nuclear receptor in which helix 12 is precisely positioned as a "lid" for the ligand-binding pocket. Binding of 9alpha-fluorocortisol to the AR(ccr) involves favorable hydrogen bond patterns on the C17 and C21 substituents of the ligand due to the mutations at 701 and 877 in the AR(ccr). Our studies provide the first structural explanation for the glucocorticoid activation of AR(ccr), which is important for the development of new therapeutic treatments for androgen-independent prostate cancer.

Reviews - 1gs4 mentioned but not cited (1)

  1. Androgen receptor: structure, role in prostate cancer and drug discovery. Tan MH, Li J, Xu HE, Melcher K, Yong EL. Acta Pharmacol Sin 36 3-23 (2015)

Articles - 1gs4 mentioned but not cited (9)

  1. A system-level investigation into the mechanisms of Chinese Traditional Medicine: Compound Danshen Formula for cardiovascular disease treatment. Li X, Xu X, Wang J, Yu H, Wang X, Yang H, Xu H, Tang S, Li Y, Yang L, Huang L, Wang Y, Yang S. PLoS One 7 e43918 (2012)
  2. Pharmacophore-based virtual screening versus docking-based virtual screening: a benchmark comparison against eight targets. Chen Z, Li HL, Zhang QJ, Bao XG, Yu KQ, Luo XM, Zhu WL, Jiang HL. Acta Pharmacol Sin 30 1694-1708 (2009)
  3. Improved docking, screening and selectivity prediction for small molecule nuclear receptor modulators using conformational ensembles. Park SJ, Kufareva I, Abagyan R. J Comput Aided Mol Des 24 459-471 (2010)
  4. Systems pharmacology to investigate the interaction of berberine and other drugs in treating polycystic ovary syndrome. Wang Y, Fu X, Xu J, Wang Q, Kuang H. Sci Rep 6 28089 (2016)
  5. Analysis of the "thermodynamic information content" of a Homo sapiens structural database reveals hierarchical thermodynamic organization. Larson SA, Hilser VJ. Protein Sci 13 1787-1801 (2004)
  6. Binding site characterization - similarity, promiscuity, and druggability. Ehrt C, Brinkjost T, Koch O. Medchemcomm 10 1145-1159 (2019)
  7. Anti-Alzheimer's Disease Molecular Mechanism of Acori Tatarinowii Rhizoma Based on Network Pharmacology. Zhang Y, Wu Y, Fu Y, Lin L, Lin Y, Zhang Y, Ji L, Li C. Med Sci Monit Basic Res 26 e924203 (2020)
  8. An integrative approach to develop computational pipeline for drug-target interaction network analysis. Bansal A, Srivastava PA, Singh TR. Sci Rep 8 10238 (2018)
  9. Cheminformatics and Machine Learning Approaches to Assess Aquatic Toxicity Profiles of Fullerene Derivatives. Fjodorova N, Novič M, Venko K, Rasulev B, Türker Saçan M, Tugcu G, Sağ Erdem S, Toropova AP, Toropov AA. Int J Mol Sci 24 14160 (2023)


Reviews citing this publication (12)

  1. Chemistry and structural biology of androgen receptor. Gao W, Bohl CE, Dalton JT. Chem Rev 105 3352-3370 (2005)
  2. PI3K-AKT-mTOR signaling in prostate cancer progression and androgen deprivation therapy resistance. Edlind MP, Hsieh AC. Asian J Androl 16 378-386 (2014)
  3. Pleiotropic functional properties of androgen receptor mutants in prostate cancer. Bergerat JP, Céraline J. Hum Mutat 30 145-157 (2009)
  4. Role of steroid receptor and coregulator mutations in hormone-dependent cancers. Groner AC, Brown M. J Clin Invest 127 1126-1135 (2017)
  5. Novel drugs targeting the androgen receptor pathway in prostate cancer. Mateo J, Smith A, Ong M, de Bono JS. Cancer Metastasis Rev 33 567-579 (2014)
  6. The role of glucocorticoid receptor in prostate cancer progression: from bench to bedside. Hu J, Chen Q. Int Urol Nephrol 49 369-380 (2017)
  7. Enzalutamide for the treatment of prostate cancer. Pal SK, Stein CA, Sartor O. Expert Opin Pharmacother 14 679-685 (2013)
  8. Structures of androgen receptor bound with ligands: advancing understanding of biological functions and drug discovery. Sakkiah S, Ng HW, Tong W, Hong H. Expert Opin Ther Targets 20 1267-1282 (2016)
  9. Androgen receptor antagonists: a patent review (2008-2011). Mohler ML, Coss CC, Duke CB, Patil SA, Miller DD, Dalton JT. Expert Opin Ther Pat 22 541-565 (2012)
  10. The significance of the 20-carbonyl group of progesterone in steroid receptor binding: a molecular dynamics and structure-based ligand design study. Hillisch A, von Langen J, Menzenbach B, Droescher P, Kaufmann G, Schneider B, Elger W. Steroids 68 869-878 (2003)
  11. Androgen and estrogen receptors: potential of crystallography in the fight against cancer. Nahoum V, Bourguet W. Int J Biochem Cell Biol 39 1280-1287 (2007)
  12. The androgen receptor for the radiation oncologist. Quero L, Rozet F, Beuzeboc P, Hennequin C. Cancer Radiother 19 220-227 (2015)

Articles citing this publication (33)

  1. Molecular determinants of resistance to antiandrogen therapy. Chen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R, Rosenfeld MG, Sawyers CL. Nat Med 10 33-39 (2004)
  2. Structural basis for antagonism and resistance of bicalutamide in prostate cancer. Bohl CE, Gao W, Miller DD, Bell CE, Dalton JT. Proc Natl Acad Sci U S A 102 6201-6206 (2005)
  3. The structural basis of androgen receptor activation: intramolecular and intermolecular amino-carboxy interactions. Schaufele F, Carbonell X, Guerbadot M, Borngraeber S, Chapman MS, Ma AA, Miner JN, Diamond MI. Proc Natl Acad Sci U S A 102 9802-9807 (2005)
  4. Comparison of crystal structures of human androgen receptor ligand-binding domain complexed with various agonists reveals molecular determinants responsible for binding affinity. Pereira de Jésus-Tran K, Côté PL, Cantin L, Blanchet J, Labrie F, Breton R. Protein Sci 15 987-999 (2006)
  5. Modulation of androgen receptor activation function 2 by testosterone and dihydrotestosterone. Askew EB, Gampe RT, Stanley TB, Faggart JL, Wilson EM. J Biol Chem 282 25801-25816 (2007)
  6. Structural basis for accommodation of nonsteroidal ligands in the androgen receptor. Bohl CE, Miller DD, Chen J, Bell CE, Dalton JT. J Biol Chem 280 37747-37754 (2005)
  7. Activity profiles of 309 ToxCast™ chemicals evaluated across 292 biochemical targets. Knudsen TB, Houck KA, Sipes NS, Singh AV, Judson RS, Martin MT, Weissman A, Kleinstreuer NC, Mortensen HM, Reif DM, Rabinowitz JR, Setzer RW, Richard AM, Dix DJ, Kavlock RJ. Toxicology 282 1-15 (2011)
  8. Androgen receptor gene mutation, rearrangement, polymorphism. Eisermann K, Wang D, Jing Y, Pascal LE, Wang Z. Transl Androl Urol 2 137-147 (2013)
  9. Discovery of antiandrogen activity of nonsteroidal scaffolds of marketed drugs. Bisson WH, Cheltsov AV, Bruey-Sedano N, Lin B, Chen J, Goldberger N, May LT, Christopoulos A, Dalton JT, Sexton PM, Zhang XK, Abagyan R. Proc Natl Acad Sci U S A 104 11927-11932 (2007)
  10. A fluorine scan of the phenylamidinium needle of tricyclic thrombin inhibitors: effects of fluorine substitution on pKa and binding affinity and evidence for intermolecular C-F...CN interactions. Olsen J, Seiler P, Wagner B, Fischer H, Tschopp T, Obst-Sander U, Banner DW, Kansy M, Müller K, Diederich F. Org Biomol Chem 2 1339-1352 (2004)
  11. Systematic structure-function analysis of androgen receptor Leu701 mutants explains the properties of the prostate cancer mutant L701H. van de Wijngaart DJ, Molier M, Lusher SJ, Hersmus R, Jenster G, Trapman J, Dubbink HJ. J Biol Chem 285 5097-5105 (2010)
  12. Interaction of organophosphate pesticides and related compounds with the androgen receptor. Tamura H, Yoshikawa H, Gaido KW, Ross SM, DeLisle RK, Welsh WJ, Richard AM. Environ Health Perspect 111 545-552 (2003)
  13. PC-3 cells with enhanced androgen receptor signaling: a model for clonal selection in prostate cancer. Buchanan G, Craft PS, Yang M, Cheong A, Prescott J, Jia L, Coetzee GA, Tilley WD. Prostate 60 352-366 (2004)
  14. C-Met/miR-130b axis as novel mechanism and biomarker for castration resistance state acquisition. Cannistraci A, Federici G, Addario A, Di Pace AL, Grassi L, Muto G, Collura D, Signore M, De Salvo L, Sentinelli S, Simone G, Costantini M, Nanni S, Farsetti A, Coppola V, De Maria R, Bonci D. Oncogene 36 3718-3728 (2017)
  15. Leupaxin, a novel coactivator of the androgen receptor, is expressed in prostate cancer and plays a role in adhesion and invasion of prostate carcinoma cells. Kaulfuss S, Grzmil M, Hemmerlein B, Thelen P, Schweyer S, Neesen J, Bubendorf L, Glass AG, Jarry H, Auber B, Burfeind P. Mol Endocrinol 22 1606-1621 (2008)
  16. Molecular determinants of the recognition of ulipristal acetate by oxo-steroid receptors. Petit-Topin I, Fay M, Resche-Rigon M, Ulmann A, Gainer E, Rafestin-Oblin ME, Fagart J. J Steroid Biochem Mol Biol 144 Pt B 427-435 (2014)
  17. Arylisothiocyanato selective androgen receptor modulators (SARMs) for prostate cancer. Hwang DJ, Yang J, Xu H, Rakov IM, Mohler ML, Dalton JT, Miller DD. Bioorg Med Chem 14 6525-6538 (2006)
  18. Proteomic-coupled-network analysis of T877A-androgen receptor interactomes can predict clinical prostate cancer outcomes between White (non-Hispanic) and African-American groups. Zaman N, Giannopoulos PN, Chowdhury S, Bonneil E, Thibault P, Wang E, Trifiro M, Paliouras M. PLoS One 9 e113190 (2014)
  19. Uncoupling of hormone-dependence from chaperone-dependence in the L701H mutation of the androgen receptor. Robzyk K, Oen H, Buchanan G, Butler LM, Tilley WD, Mandal AK, Rosen N, Caplan AJ. Mol Cell Endocrinol 268 67-74 (2007)
  20. Classification and comparison of ligand-binding sites derived from grid-mapped knowledge-based potentials. Hoppe C, Steinbeck C, Wohlfahrt G. J Mol Graph Model 24 328-340 (2006)
  21. Docking and CoMSIA studies on steroids and non-steroidal chemicals as androgen receptor ligands. Wang X, Li X, Shi W, Wei S, Giesy JP, Yu H, Wang Y. Ecotoxicol Environ Saf 89 143-149 (2013)
  22. Conformational dynamics of androgen receptors bound to agonists and antagonists. Gim HJ, Park J, Jung ME, Houk KN. Sci Rep 11 15887 (2021)
  23. Phase II trial of thalidomide and daily oral dexamethasone for treatment of hormone refractory prostate cancer progressing after chemotherapy. Romero S, Stanton G, DeFelice J, Schreiber F, Rago R, Fishman M. Urol Oncol 25 284-290 (2007)
  24. A multi-parameter imaging assay identifies different stages of ligand-induced androgen receptor activation. van Royen ME, van de Wijngaart DJ, Cunha SM, Trapman J, Houtsmuller AB. Cytometry A 83 806-817 (2013)
  25. Bile acids and their oxo derivatives: Potential inhibitors of carbonic anhydrase I and II, androgen receptor antagonists and CYP3A4 substrates. Trifunović J, Borčić V, Mikov M. Biomed Chromatogr 31 (2017)
  26. Chemical synthesis and biological activities of 16alpha-derivatives of 5alpha-androstane-3alpha,17beta-diol as antiandrogens. Roy J, Breton R, Martel C, Labrie F, Poirier D. Bioorg Med Chem 15 3003-3018 (2007)
  27. Perspectives on designs of antiandrogens for prostate cancer. Estébanez-Perpiñá E, Jouravel N, Fletterick RJ. Expert Opin Drug Discov 2 1341-1355 (2007)
  28. A dramatic, objective antiandrogen withdrawal response: case report and review of the literature. Lau YK, Chadha MK, Litwin A, Trump DL. J Hematol Oncol 1 21 (2008)
  29. Lncap-AI prostate cancer cell line establishment by Flutamide and androgen-free environment to promote cell adherent. Wang H, Wei X, Zhang D, Li W, Hu Y. BMC Mol Cell Biol 23 51 (2022)
  30. Multiple Docetaxel Retreatments Without Prednisone for Metastatic Castration-Resistant Prostate Cancer in the Docetaxel-Only Era: Effects on PSA Kinetics and Survival. Maj-Hes A, Szarvas T, Sevcenco S, Kramer G. Adv Ther 38 3831-3841 (2021)
  31. Structural classification of steroid-binding sites on proteins by coarse-grained atomic environment and its correlation with their biological function. Hori-Tanaka Y, Yura K, Takai-Igarashi T, Tanaka H. Steroids 96 81-88 (2015)
  32. A partially open conformation of an androgen receptor ligand-binding domain with drug-resistance mutations. Doamekpor SK, Peng P, Xu R, Ma L, Tong Y, Tong L. Acta Crystallogr F Struct Biol Commun 79 95-104 (2023)
  33. N'-(4-Fluoro-benzyl-idene)-2-(4-fluoro-phen-yl)acetohydrazide. Fun HK, Hemamalini M, Sumangala V, Nagaraja GK, Poojary B. Acta Crystallogr Sect E Struct Rep Online 67 o2835 (2011)


Quick links