A Structural Switch Between Agonist and Antagonist Bound Conformations for a Ligand-Optimized Model of the Human Aryl Hydrocarbon Receptor Ligand Binding Domain

Biology

Volumn 3, Issue 4, 2014, Pages 645-669

  Perkins, Arden ^a   Phillips, Jessica L ^a,b   Kerkvliet, Nancy I ^a   Tanguay, Robert L ^a   Perdew, Gary H ^c   Kolluri, Siva K ^a,b   Bisson, William H ^a  

^a OREGON STATE UNIVERSITY   (United States)

^b Cancer Research Laboratory   (United States)

^c PENNSYLVANIA STATE UNIVERSITY   (United States)

Author keywords

Agonist; Antagonist; Aryl hydrocarbon receptor; HSP90; Ligand binding domain; Ligand guided optimization; Molecular dynamics; Virtual ligand screening

Indexed keywords

EID: 84908306436     PISSN: None     EISSN: 20797737     Source Type: Journal    
DOI: 10.3390/biology3040645     Document Type: Article

References (42)

1. Beischlag, T.V.; Morales, J.L.; Hollingshead, B.D.; Perdew, G.H. The aryl hydrocarbon receptor complex and the control of gene expression. Crit. Rev. Eukaryot. Gene Expr. 2008, 18, 207-250.
2. Ma, C.; Marlowe, J.L.; Puga, A. The aryl hydrocarbon receptor at the crossroads of multiple signaling pathways. Mol. Clin. Environ. Toxicol. Experientia Suppl. 2009, 99, 231-257.
3. Nguyen, L.P.; Bradfield, C.A. The search for endogenous activators of the aryl hydrocarbon receptor. Chem. Res. Toxicol. 2008, 21, 102-116.
4. Petrulis, J.R.; Perdew, G.H. The role of chaperone proteins in the aryl hydrocarbon receptor core complex. Chem. Biol. Interact. 2002, 141, 25-40.
5. Smith, K.J.; Murray, I.A.; Tanos, R.S.; Tellew, J.; Boitano, A.E.; Bisson, W.H.; Kolluri, S.K.; Cooke, M.P.; Perdew, G.H. Identification of a high-affinity ligand that exhibits complete aryl hydrocarbon receptor antagonism. J. Pharmacol. Exp. Ther. 2011, 338, 318-327.
6. Bisson, W.H.; Koch, D.; O'Donnell, E.F.; Kerkvliet, N.I.; Tanguay, R.L.; Abagyan, R.; Kolluri, S.K. Modeling of the aryl hydrocarbon receptor (AhR) ligand binding domain and its utility in virtual ligand screening to predict new AhR ligands. J. Med. Chem. 2009, 52, 5635-5641.
7. Boitano, A.E.; Wang, J.; Romeo, R.; Bouchez, L.C.; Parker, A.E.; Sutton, S.E.; Walker, J.R.; Flaveny, C.A.; Perdew, G.H.; Denison, M.S.; et al. Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science 2010, 329, 1345-1348.
8. Lin, T.-M.; Ko, K.; Moore, R.W.; Simanainen, U.; Oberley, T.D.; Peterson R.E. Effects of aryl hydrocarbon receptor null mutation and in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on prostate and seminal vesicle development in C57BL/6 mice. Toxicol. Sci. 2002, 68, 479-487.
9. O'Donnell, E.F.; Saili, K.S.; Koch, D.C.; Kopparapu, P.R.; Farrer, D.; Bisson, W.H.; Mathew, L.K.; Sengupta, S.; Kerkvliet, N.I.; Tanguay, R.L.; et al. The anti-infiammatory drug Leflunomide is an agonist of the Aryl Hydrocarbon Receptor. PLoS One 2010, 5, e13128.
10. O'Donnell, E.F.; Koch, D.; Bisson, W.H.; Yang, H.-S.; Kolluri, S.K. The aryl hydrocarbon receptor mediates raloxifene-induced apoptosis in estrogen receptor negative hepatoma and breast cancer cells. Cell Death Dis. 2014, 5, e1038.
11. Di Natale, B.C.; Smith, K.; John, K.; Krishnegowda, G.; Amin, S.G.; Perdew, G.H. Ah receptor antagonism represses head and neck tumor cell aggressive phenotype. Mol. Cancer Res. 2012, 10, 1369-1379.
12. Lahoti, T.S.; John, K.; Hughes, J.M.; Kusnadi, A.; Murray, I.A.; Krishnegowda, G.; Amin, S.; Perdew, G.H. Aryl hydrocarbon receptor antagonism mitigates cytokine-mediated inflammatory signalling in primary human fibroblast-like synoviocytes. Ann. Rheum. Dis. 2013, 72, 1708-1716.
13. Motto, I.; Bordogna, A.; Soshilov, A.A.; Denison, M.S.; Bonati, L. New aryl hydrocarbon receptor homology model targeted to improve docking reliability. J. Chem. Inf. Model. 2011, 51, 2868-2881.
14. Bessede, A.; Gargaro, M.; Pallotta, M.T.; Matino, D.; Servillo, G.; Brunacci, C.; Bicciato, S.; Mazza, E.M.; Macchiarulo, A.; Vacca, C.; et al. Aryl hydrocarbon receptor control of a disease tolerance defence pathway. Nature 2014, 511, 184-190.
15. Erbel, P.J.A.; Card, P.B.; Karakuzu, O.; Bruick, R.K.; Gardner, K.H. Structural basis for PAS domain heterodimerization in the basic helix-loop-helix-PAS transcription factor hypoxia-inducible factor. Proc. Natl. Acad. Sci. USA 2003, 100, 15504-15509.
16. Scheuermann, T.H.; Tomchick, D.R.; Machius, M.; Guo, Y.; Bruick, R.K.; Gardner, K.H. Artificial ligand binding within the HIF2alpha PAS-B domain of the HIF2 transcription factor. Proc. Natl. Acad. Sci. USA 2009, 106, 450-455.
17. Fraccalvieri, D.; Soshilov, A.A.; Karchner, S.I.; Franks, D.G.; Pandini, A.; Bonati, L.; Hahn, M.E.; Denison, M.S. Comparative analysis of homology models of the ah receptor ligand binding domain: Verification of structure-Function predictions by site-directed mutagenesis of a nonfunctional receptor. Biochemistry 2013, 52, 714-725.
18. Pandini, A.; Soshilov, A.A.; Song, Y.; Zhao, J.; Bonati, L.; Denison, M.S. Detection of the TCDD binding-fingerprint within the Ah receptor ligand binding domain by structurally driven mutagenesis and functional analysis. Biochemistry 2009, 48, 5972-5983.
19. Gerlach, C.V.; Das, S.R.; Volz, D.C.; Bisson, W.H.; Kolluri, S.K.; Tanguay, R.L. Mono-substituted isopropylated triaryl phosphate, a major component of Firemaster 550, is an AHR agonist that exhibits AHR-independent cardiotoxicity in zebrafish. Aquat. Tox. 2014, 154, 71-79.
20. Key, J.; Scheuermann, T.H.; Anderson, P.C.; Daggett, V.; Gardner, K.H. Principles of ligand binding within a completely buried cavity in HIF2_ PAS-B. J. Am. Chem. Soc. 2009, 131, 17647-17654.
21. Abagyan, R.; Totrov, M.; Kuznetsov, D. ICM-A new method for protein modeling and design: applications to docking and structure prediction from the distorted native conformation. J. Comput. Chem. 1994, 15, 488-506.
22. Neves, M.A.C.; Totrov, M.; Abagyan, R. Docking and scoring with ICM: The benchmarking results and strategies for improvement. J. Comput. Aided Mol. Des. 2012, 26, 675-686.
23. Katritch, V.; Rueda, M.; Abagyan, R. Ligand-guided receptor optimization. In Homology Modeling; Orry, A.J.W., Abagyan, R., Eds; Humana Press: Totowa, NJ, USA, 2012; Volume 857, pp. 189-205.
24. Maiorov, V.; Abagyan, R. Energy strain in three-dimensional protein structures. Fold. Des. 1998, 3, 259-269.
25. Flaveny, C.A.; Murray, I.A.; Perdew, G.H. differential gene regulation by the human and mouse aryl hydrocarbon receptor. Toxicol. Sci. 2010, 114, 217-225.
26. Schroeder, J.C.; Dinatale, B.C.; Murray, I.A.; Flaveny, C.A.; Liu, Q.; Laurenzana, E.M.; Lin, J.M.; Strom, S.C.; Omiecinski, C.J.; Amin, S.; et al. The uremic toxin 3-indoxyl sulfate is a potent endogenous agonist for the human aryl hydrocarbon receptor. Biochemistry 2010, 49, 393-400.
27. Basham, K.J.; Kieffer, C.; Shelton, D.N.; Leonard, C.J.; Bhonde, V.R.; Vankayalapati, H.; Milash, B.; Bearss, D.J.; Looper, R.E.; Welm, B.E. Chemical genetic screen reveals a role for desmosomal adhesion in mammary branching morphogenesis. J. Biol. Chem. 2013, 288, 2261-2270.
28. Jin, U.-H.; Lee, S.; Safe, S. Aryl hydrocarbon receptor (AHR)-active pharmaceuticals are selective AHR modulators in MDA-MB-468 and BT474 breast cancer cells. J. Pharmacol. Exp. Ther. 2012, 343, 333-341.
29. Wang, J.; Wang, W.; Kollman, P.A.; Case, D.A. Antechamber: An accessory software package for molecular mechanical calculations. J. Am. Chem. Soc. 2001, 222, U403.
30. Di Nola, A.; Roccatano, D.; Berendsen, H.J.C. Molecular dynamics simulation of the docking of substrates to proteins. Proteins Struct. Funct. Bioinforma. 1994, 19, 174-182.
31. Case, D.A.; Darden, T.A.; Cheatham T.E., III; Simmerling, C.L.; Wang, J.; Duke, R.E.; Luo, R.; Walker, R.C.; Zhang, W.; Merz, K.M. AMBER 12; University of California: San Francisco, CA, USA, 2012.
32. Mittag, T.; Kay, L.E.; Forman-Kay, J.D. Protein dynamics and conformational disorder in molecular recognition. J. Mol. Recognit. 2010, 23, 105-116.
33. Humphrey, W.; Dalke, A.; Schulten, K. VMD: Visual molecular dynamics. J. Mol. Graph. 1996, 14, 33-38.
34. Murray, I.A.; Flaveny, C.A.; Chiaro, C.R.; Sharma, A.K.; Tanos, R.S.; Schroeder, J.C.; Amin, S.G.; Bisson, W.H.; Kolluri, S.K.; Perdew, G.H. Suppression of cytokine-mediated complement factor gene expression through selective activation of the Ah receptor with 3',4'-dimethoxy-_-naphthoflavone. Mol. Pharmacol. 2011, 79, 508-519.
35. Heifetz, A.; Barker, O.; Morris, G.B.; Law, R.J.; Slack, M.; Biggin, P.C. Toward an understanding of agonist binding to human orexin-1 and orexin-receptors with g- protein-coupled receptor modeling and site-directed mutagenesis. Biochemistry 2013, 52, 8246-8260.
36. Katritch, V.; Cherezov, V.; Stevens, R.C. Diversity and modularity of G-protein-coupled receptor structures. Trends Pharmacol. Sci. 2012, 33, 17-27.
37. Toxicology in the 21st Century. Available online: http://www.ncats.nih.gov/research/reengineering/ tox21/tox21.html (accessed on 20 November 2013).
38. Kavlock, R.; Dix, D. Computational toxicology as implemented by the U.S. EPA: Providing high throughput decision support tools for screening and assessing chemical exposure, hazard and risk. J. Toxicol. Environ. Health B 2010, 13, 197-217.
39. Bisson, W.H.; Abagyan, R.; Cavasotto, C.N. Molecular basis of agonicity and antagonicity in the androgen receptor studied by molecular dynamics simulations. J. Mol. Graph. Model. 2008, 27, 452-458.
40. Crosson, S.; Moffat, K. Structure of a flavin-binding plant photoreceptor domain: Insights into light-mediated signal transduction. Proc. Natl. Acad. Sci. USA 2001, 98, 2995-3000.
41. Hoff, W.D.; Xie, A.; van Stokkum, I.H.; Tang, X.J.; Gural, J.; Kroon, A.R.; Hellingwerf, K.J. Global conformational changes upon receptor stimulation in photoactive yellow protein. Biochemistry 1999, 38, 1009-1017.
42. Soshilov, A.A.; Denison, M.S. Ligand promiscuity of aryl hydrocarbon receptor agonists and antagonists revealed by site-directed mutagenesis. Mol. Cell Biol. 2014, 34, 1707-1719.