Adaptability of the Vitamin D nuclear receptor to the synthetic ligand Gemini: Remodelling the LBP with one side chain rotation

被引：77

作者：

Ciesielski, Fabrice ^{[1
]}

Rochel, Natacha ^{[1
]}

Moras, Dino ^{[1
]}

机构：

[1] Univ Strasbourg 1, Dept Biol & Genom Struct, IGBMC, CNRS INSERM, F-67404 Illkirch Graffenstaden, France

来源：

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY | 2007年 / 103卷 / 3-5期

关键词：

1; alpha; 25(OH)(2)D-3; Gemini; vitamin D receptor; crystal structure; adaptability;

D O I：

10.1016/j.jsbmb.2006.12.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The crystal structure of the ligand binding domain (LBD) of the wild-type Vitamin D receptor (VDR) of zebrafish bound to Gemini, a synthetic agonist ligand with two identical side chains branching at carbon 20 reveals a ligand-dependent structural rearrangement of the ligand binding pocket (LBP). The rotation of a Leu side chain opens the access to a channel that can accommodate the second side chain of the ligand. The 25% increase of the LBP's volume does not alter the essential agonist features of VDR. The possibility to adapt the LBP to novel ligands with different chemistry and/or structure opens new perspectives in the design of more specifically targeted ligands. (c) 2006 Elsevier Ltd. All rights reserved.

引用

收藏

页码：235 / 242

页数：8

相关论文

共 36 条

[1] Structural adaptability in the ligand-binding pocket of the ecdysone hormone receptor [J].

Billas, IML ;

Iwema, T ;

Garnier, JM ;

Mitschler, A ;

Rochel, N ;

Moras, D .

NATURE, 2003, 426 (6962) :91-96

[2] Ligand selectivity by seeking hydrophobicity in thyroid hormone receptor [J].

Borngraeber, S ;

Budny, MJ ;

Chiellini, G ;

Cunha-Lima, ST ;

Togashi, M ;

Webb, P ;

Baxter, JD ;

Scanlan, TS ;

Fletterick, RJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (26) :15358-15363

[3]

Bouillon R, 2003, RECENT RES CANCER, V164, P353

[4] Crystallography & NMR system:: A new software suite for macromolecular structure determination [J].

Brunger, AT ;

Adams, PD ;

Clore, GM ;

DeLano, WL ;

Gros, P ;

Grosse-Kunstleve, RW ;

Jiang, JS ;

Kuszewski, J ;

Nilges, M ;

Pannu, NS ;

Read, RJ ;

Rice, LM ;

Simonson, T ;

Warren, GL .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 :905-921

[5]

Bury Y, 2001, J CELL BIOCHEM, P179

[6] Molecular basis of the selective activity of vitamin D analogues [J].

Carlberg, C .

JOURNAL OF CELLULAR BIOCHEMISTRY, 2003, 88 (02) :274-281

[7] Interaction between vitamin D receptor and vitamin D ligands: Two-dimensional alanine scanning mutational analysis [J].

Choi, M ;

Yamamoto, K ;

Itoh, T ;

Makishima, M ;

Mangelsdorf, DJ ;

Moras, D ;

DeLuca, HF ;

Yamada, S .

CHEMISTRY & BIOLOGY, 2003, 10 (03) :261-270

[8] Structural disorder in the complex of human pregnane X receptor and the macrolide antibiotic rifampicin [J].

Chrencik, JE ;

Orans, J ;

Moore, LB ;

Xue, Y ;

Peng, L ;

Collins, JL ;

Wisely, GB ;

Lambert, MH ;

Kliewer, SA ;

Redinbo, MR .

MOLECULAR ENDOCRINOLOGY, 2005, 19 (05) :1125-1134

[9] Structural investigation of the ligand binding domain of the zebrafish VDR in complexes with 1α,25(OH)2D3 and Gemini:: purification, crystallization and preliminary X-ray diffraction analysis [J].

Ciesielski, F ;

Rochel, N ;

Mitschler, A ;

Kouzmenko, A ;

Moras, D .

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2004, 89-90 (1-5) :55-59

[10] Structure and specificity of nuclear receptor-coactivator interactions [J].

Darimont, BD ;

Wagner, RL ;

Apriletti, JW ;

Stallcup, MR ;

Kushner, PJ ;

Baxter, JD ;

Fletterick, RJ ;

Yamamoto, KR .

GENES & DEVELOPMENT, 1998, 12 (21) :3343-3356

← 1 2 3 4 →