PMID: 11906285Mar 22, 2002Paper

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

Journal of Medicinal Chemistry
P M MatiasP Donner

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.

References

May 25, 1977·Journal of Molecular Biology·F C BernsteinM Tasumi
Oct 24, 1997·Nature·A M BrzozowskiM Carlquist
Mar 10, 1998·Journal of Computer-aided Molecular Design·I J BrunoM L Verdonk
Jun 10, 1998·Nature·S P Williams, P B Sigler
Jun 3, 2000·Nature Medicine·A O Brinkmann, J Trapman
Jun 7, 2000·Proceedings of the National Academy of Sciences of the United States of America·B P KlaholzD Moras
Jan 1, 1997·Methods in Enzymology·V S Lamzin, K S Wilson
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

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Citations

Aug 29, 2012·Journal of Chemical Information and Modeling·Eleonora Gianti, Randy J Zauhar
Sep 15, 2005·Chemical Reviews·Wenqing GaoJames T Dalton
Dec 17, 2009·The Journal of Biological Chemistry·Dennis J van de WijngaartHendrikus J Dubbink
Sep 1, 2005·The Journal of Biological Chemistry·Casey E BohlJames T Dalton
Jan 6, 2012·Acta Crystallographica. Section E, Structure Reports Online·Hoong-Kun FunBoja Poojary
Jan 6, 2012·Acta Crystallographica. Section E, Structure Reports Online·Hoong-Kun FunBoja Poojary
Jan 6, 2012·Acta Crystallographica. Section E, Structure Reports Online·Jirapa HorkaewHoong-Kun Fun
Nov 7, 2008·Journal of Hematology & Oncology·Yiu-Keung LauDonald L Trump
Apr 5, 2003·Environmental Health Perspectives·Hiroto TamuraAnn M Richard
Jul 4, 2007·Proceedings of the National Academy of Sciences of the United States of America·W H BissonR Abagyan
Jul 5, 2005·Proceedings of the National Academy of Sciences of the United States of America·Fred SchaufeleMarc I Diamond
Apr 25, 2014·Asian Journal of Andrology·Merritt P Edlind, Andrew C Hsieh
Apr 19, 2005·Proceedings of the National Academy of Sciences of the United States of America·Casey E BohlJames T Dalton
Jan 7, 2014·Cancer Metastasis Reviews·Joaquin MateoJohann S de Bono
Oct 1, 2007·Expert Opinion on Drug Discovery·Eva Estébanez-PerpiñáRobert J Fletterick
Sep 19, 2008·Human Mutation·Jean-Pierre Bergerat, Jocelyn Céraline
Dec 25, 2012·Ecotoxicology and Environmental Safety·Xiaoxiang WangYulei Wang
Jan 22, 2011·Toxicology·Thomas B KnudsenRobert J Kavlock
Mar 6, 2007·Molecular and Cellular Endocrinology·Kenneth RobzykAvrom J Caplan
Feb 16, 2007·The International Journal of Biochemistry & Cell Biology·Virginie Nahoum, William Bourguet
Nov 2, 2005·Journal of Molecular Graphics & Modelling·Christian HoppeGerd Wohlfahrt
Sep 11, 2014·The Journal of Steroid Biochemistry and Molecular Biology·I Petit-TopinJ Fagart
Feb 28, 2013·Expert Opinion on Pharmacotherapy·Sumanta K PalOliver Sartor
May 16, 2012·Expert Opinion on Therapeutic Patents·Michael L MohlerJames T Dalton
Apr 30, 2015·Cancer radiothérapie : journal de la Société française de radiothérapie oncologique·L QueroC Hennequin
Jun 10, 2014·Acta Pharmacologica Sinica·Mh Eileen TanEu-Leong Yong
May 20, 2016·Expert Opinion on Therapeutic Targets·Sugunadevi SakkiahHuixiao Hong
Dec 18, 2016·International Urology and Nephrology·Jieping Hu, Qingke Chen
Nov 24, 2018·Chemical Biology & Drug Design·Mira AhinkoOlli T Pentikäinen
Jan 2, 2004·Nature Medicine·Charlie D ChenCharles L Sawyers
Apr 16, 2013·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Martin E van RoyenAdriaan B Houtsmuller
Nov 21, 2002·The Journal of Biological Chemistry·Guoqing LiaoJ Don Chen
Jul 20, 2007·Molecular Endocrinology·Scott M Dehm, Donald J Tindall
Apr 4, 2017·The Journal of Clinical Investigation·Anna C Groner, Myles Brown
Jun 27, 2007·The Journal of Biological Chemistry·Emily B AskewElizabeth M Wilson
Nov 9, 2005·Molecular Cancer Therapeutics·Romyla IlaganMichael Carey
Nov 24, 2006·Molecular Cancer Therapeutics·Ang LiuRichard B van Breemen
May 20, 2016·Molecular Cancer Therapeutics·Stefan PrekovicChristine Helsen
Jan 20, 2020·Molecular Aspects of Medicine·Delila Gasi Tandefelt, Johann de Bono

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