Analysis of crystal structures of LXRβ in relation to plasticity of the ligand-binding domain upon ligand binding

Chemical Biology and Drug Design

Volumn 71, Issue 2, 2008, Pages 140-154

  Malini, Nagulapalli ^a   Rajesh, Hariharan ^a   Berwal, Pooja ^a   Phukan, Samiron ^a   Balaji, Vittukudi Narayanaiyengar ^a  

^a JUBILANT BIOSYS LTD   (India)

Author keywords

LXR ; Plasticity of ligand binding domain; Protein ligand analysis

Indexed keywords

HISTIDINE; LEUCINE; LIVER X RECEPTOR; PHENYLALANINE; TRYPTOPHAN;

AMINO ACID SEQUENCE; ARTICLE; CRYSTAL STRUCTURE; PLASTICITY; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN STRUCTURE; X RAY CRYSTALLOGRAPHY;

BINDING SITES; CRYSTALLOGRAPHY, X-RAY; DNA-BINDING PROTEINS; DRUG DESIGN; HUMANS; LIGANDS; MOTION; PLIABILITY; PROTEIN BINDING; PROTEIN CONFORMATION; RECEPTORS, CYTOPLASMIC AND NUCLEAR; SUBSTRATE SPECIFICITY;

EID: 38549119329     PISSN: 17470277     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1747-0285.2007.00620.x     Document Type: Article

References (18)

1. Schultz J.R., Tu H., Luk A., Repa J.J., Medina J.C., Li L., Schwendner S. et al. (2000) Role of LXRs in control of lipogenesis. Genes Dev 14 : 2831 2838.
2. Svensson S., Ostberg T., Jacobsson M., Norstrom C., Stefansson K., Hallen D., Johansson I.C. et al. (2003) Crystal structure of the heterodimeric complex of LXRalpha and RXRbeta ligand-binding domains in a fully agonistic conformation. EMBO J 22 : 4625 4633.
3. Liu W., Chen S., Dropinski J., Colwell L., Robins M., Szymonifka M., Hayes N. et al. (2005) Design, synthesis, and structure-activity relationship of podocarpic acid amides as liver X receptor agonists for potential treatment of atherosclerosis. Bioorg Med Chem Lett 15 : 4574 4578.
4. Joseph S.B., McKilligin E., Pei L., Watson M.A., Collins A.R., Laffitte B.A., Chen M. et al. (2002) Synthetic LXR ligand inhibits the development of atherosclerosis in mice. Proc Natl Acad Sci USA 99 : 7604 7609.
5. Zhang-Gandhi C.X., Drew P.D. (2007) Liver X receptor and retinoid X receptor agonists inhibit inflammatory responses of microglia and astrocytes. J Neuroimmunol 183 : 50 59.
6. Wente W., Brenner M.B., Zitzer H., Gromada J., Efanov A.M. (2007) Activation of liver X receptors and retinoid X receptors induces growth arrest and apoptosis in insulin-secreting cells. Endocrinology 148 : 1843 1849.
7. Lazar M.A., Willson T.M. (2007) Sweet dreams for LXR. Cell Metab 5 : 159 161.
8. Mitro N., Mak P.A., Vargas L., Godio C., Hampton E., Molteni V., Kreusch A. et al. (2007) The nuclear receptor LXR is a glucose sensor. Nature 445 : 219 223.
9. Lund E.G., Menke J.G., Sparrow C.P. (2003) Liver X receptor agonists as potential therapeutic agents for dyslipidemia and atherosclerosis. Arterioscler Thromb Vasc Biol 23 : 1169 1177.
10. Zelcer N., Tontonoz P. (2006) Liver X receptors as integrators of metabolic and inflammatory signaling. J Clin Invest 116 : 607 614.
11. Farnegardh M., Bonn T., Sun S., Ljunggren J., Ahola H., Wilhelmsson A., Gustafsson J.A. et al. (2003) The three-dimensional structure of the liver X receptor beta reveals a flexible ligand-binding pocket that can accommodate fundamentally different ligands. J Biol Chem 278 : 38821 38828.
12. Williams S., Bledsoe R.K., Collins J.L., Boggs S., Lambert M.H., Miller A.B., Moore J. et al. (2003) X-ray crystal structure of the liver X receptor beta ligand binding domain: regulation by a histidine-tryptophan switch. J Biol Chem 278 : 27138 27143.
13. Berman H.M., Battistuz T., Bhat T.N., Bluhm W.F., Bourne P.E., Burkhardt K., Feng Z. et al. (2002) The Protein Data Bank. Acta Crystallogr D Biol Crystallogr 58 : 899 907.
14. Hoerer S., Schmid A., Heckel A., Budzinski R.M., Nar H. (2003) Crystal structure of the human liver X receptor beta ligand-binding domain in complex with a synthetic agonist. J Mol Biol 334 : 853 861.
15. Thompson J.D., Higgins D.G., Gibson T.J. (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22 : 4673 4680.
16. Laskowski R.A., Hutchinson E.G., Michie A.D., Wallace A.C., Jones M.L., Thornton J.M. (1997) PDBsum: a Web-based database of summaries and analyses of all PDB structures. Trends Biochem Sci 22 : 488 490.
17. Spencer T.A., Li D., Russel J.S., Collins J.L., Bledsoe R.K., Consler T.G., Moore L.B. et al. (2001) Pharmacophore analysis of the nuclear oxysterol receptor LXRalpha. J Med Chem 44 : 886 897.
18. Ramachandran G.N., Sasisekharan V. (1968) Conformation of polypeptides and proteins. Advan Prot Chem 23 : 283 437.