DFT Calculation of Nitrogen Chemical Shifts in the Active Site of Vitamin D Receptor

• Autorzy: Sicińska W.
• Konferencja: 1st Symp. on NMR in Chemistry, Biology and Medicine; 8-10 Semptember, Warsaw, Poland. Issue dedicated to honour Prof. Witanowski
• Języki publikacji: EN

Abstrakty

EN

The complexed vitamin D receptor (VDR) is responsible for calcium homeostasis. Tryptophan is of special importance for the receptor's functions, as it appears just once in the VDR sequence and occupies the center of the ligand binding pocket. DFT calculations of nitrogen chemical shifts for Trp-NHSC moiety, presented in thiswork for liganded and free receptor, agree with NMR studies on the VDR specifically labeled with [UL] 15N2 Trp. Our calculations confirm orientation of the C(7)=C(8) vitaminDbond under the tryptophan ring. We suggest that interactions with water molecules are responsible for observed deshielding of indole Trp-nitrogen in unliganded VDR.

Słowa kluczowe

EN

nuclear receptors; vitamin D receptor; protein ligand interactions; DFT calculations of nitrogen chemical shifts

• Wydawca: Polskie Towarzystwo Chemiczne
• Czasopismo: Polish Journal of Chemistry
• Rocznik: 2006
• Tom: Vol. 80, nr 7
• Strony: 1171--1183
• Opis fizyczny: Bibliogr. 24 poz., rys.

Twórcy

autor

Sicińska W.

• Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland

Bibliografia

• 1. Evans R.M., Science, 240, 889 (1988).
• 2. Wagner R.L., Apriletti J.W., McGrath M.E., West B.L., Baxter J.D and Fletterick R. J., Nature, 378,690 (1995).
• 3, Renaud J.R, Rochel N., Ruff M., Vivat V., Chambon R, Gronemeyer H. And Moras D. D.,Nature,378,68l
• 4. Bourguet W., Ruff M., Chambon R, Gronemeyer H. And Moras D., Nature, 375,377 (1995).
• 5. Rochel N., Wurtz J.M., Mitschler A., Klaholz B. and Moras D., Mol. Cell., 5, 173 (2000).
• 6. Vanhooke J.L., Benning M.M., Bauer C.B., Pike J.W. and DeLuca H.F., Biochemistry, 43,4101 (2004).
• 7. Yamamoto K., Masuno H., Choi M., Nakashima K., Taga T., Ooizumi H., Umesono K., Sicińska W., Vanhooke J., DeLuca H.F. and Yamada S., PNAS, 97, 1467 (2000).
• 8. Wider G. and Wuthrich K., Curr. Opin. Struct. Biol., 9, 594 (1999).
• 9. Sicińska W., Westler W.M. and DeLuca H.F., Proteins, 61, 461 (2005).
• 10. Siciński R.R., Prahl J.M. and Smith C.M., J. Med. Chem., 41, 4662 (1998).
• 11. Siciński R.R., Rotkiewicz P., Koliński A., Sicińska W., Prahl J.M., Smith C.M. and DeLuca H.F., J. Med. Chem., 45, 3366 (2002).
• 12. Nguyen T.M., Adiceam P., Kottler M.L., Guillozo H., Rizk-Rabin M., Brouillard F., Lagier R, Palix C.,Garnier J.M. and Garabedian M., J. Bone. Miner. Res., 17, 1728 (2002).
• 13. Rotkiewicz R, Sicińska W., Koliński A. and DeLuca H.F., Proteins, 44, 188 (2001).
• 14. Choi M., Yamamoto K., Itoh T., Makishima M., Mangelsdorf D.J., Moras D., DeLuca H.F. and Yamada S.,Chem. Biol., 10,261(2003).
• 15. Becke A.D., Phys. Rev., A38, 3098 (1988).
• 16. Lee C., Yang W. and Parr R.G., Phys. Rev., B37, 785 (1988).
• 17. Miehlich B., Savin A., Stoll H. and Preuss H., Chem. Phys. Lett., 157, 200 (1989).
• 18. Becke A.D., J. Phys. Chem., 98, 5648 (1993).
• 19. London F., J. Phys. Radium., 8, 397 (1937).
• 20. Woliński K., Hinton J.F. and Pulay R, J. Am. Chem. Soc., 112, 8251 (1990).
• 21. Sicińska W., Rotkiewicz P. and DeLuca H.F., Proceedings of the 12th Workshop on Vitamin D, in J. Steroid Biochem. Mol. Biol, 89-90, 107 (2004).
• 22. Gaussian 03. Revision B.04, M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, J.A. Montgomery Jr., T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam, S.S. Lyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N.A. Rega, H. Petersson, M. Nakatsuji, M. Hada, K. Ehara, R. Toyota, J. Fukuda, G. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J.E. Knox, H.P. Hratchian, J.B. Cross, C. Adamo, J. Jaramillo, R. Gomperts,R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y. Ayala, K. Morokuma, G.A. Yoth, P. Salvador, J.J. Dannenberg, V.G. Zakrzewski, S. Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J. Cioslowski, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, M. Challacombe, P.M.W. Gili, B. Johnson, W. Chen, M.W. Wong, C. Gonzalez and J.A. Pople, Gaussian, Inc., Pittsburgh PA, (2003).
• 23. SYBYL Modeling Program, 7.0 ed. Tripos Inc., St. Louis, MO.
• 24. Rotkiewicz R, Biodesigner, Molecular Modeling and Visualization Program http://www.pirx.com