[en] Melatonin is a neurohormone synthesized and secreted mainly during the dark period of the circadian cycle by the pineal gland. It has already been proved to be involved in a number of chronobiological processes, most of them being mediated by its membranar receptors MT1 and MT2. Both are members of the GPCR class and, despite the interest they elicit, their 3D structure is still to be described. Models for both human MT1 and MT2 receptors have been constructed by homology modeling, using the X-ray structure of bovine rhodopsin as template. These models have been evaluated in terms of hydrophobic properties of the helices and refined to take into account the rearrangement of GPCRs necessary for their activation, thus leading to a putative activated model for each subtype.
Research Center/Unit :
Laboratoire de Chimie Thérapeutique, Université de Lille Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
In: Dubocovich M.L., Cardinali D.P., Delagrange P., Krause D.N., Strosberg A.D., Sugden D., and Yocca F.D. (Eds). The IUPHAR Compendium of Receptor Characterisation and Classification (2000), IUPHAR Media, London 270-277
Nosjean O., Ferro M., Cogé F., Beauverger P., Henlin J.-M., Lefoulon F., Fauchère J.-L., Delagrange P., Canet E., and Boutin J.A. J. Biol. Chem. 275 (2000) 31311-31317
Nosjean O., Nicolas J.-P., Klupsch F., Delagrange P., Canet E., and Boutin J.A. Biochem. Pharmacol. 61 (2001) 1369-1379
Ebisawa T., Karne S., Lerner M.R., and Reppert S.M. Proc. Natl. Acad. Sci. U.S.A. 91 (1994) 6133-6137
Li P.-K., and Witt-Enderby P.A. Drugs Future 25 (2000) 945-957
Witt-Enderby P.A., Bennett J., Jarzynka M.J., Firestine S., and Melan M.A. Life Sci. 72 (2003) 2183-2198
Drews J. Science 287 (2000) 1960-1964
Hopkins A.L., and Groom C.R. Nat. Rev. Drug Discov. 1 (2002) 727-730
Klabunde T., and Hessler G. ChemBioChem 3 (2002) 928-944
Oliveira L., Paiva A.C.M., Sander C., and Vriend G. Trends Pharmacol. Sci. 15 (1994) 170-172
Kokkola T., Watson M.-A., White J., Dowell S., Foord S.M., and Laitinen J.T. Biochem. Biophys. Res. Commun. 249 (1998) 531-536
White S.H., Ladokhin A.S., Jayasinghe S., and Hristova K. J. Biol. Chem. 276 (2001) 32395-32398
Stenkamp R.E., Teller D.C., and Palczewski K. Arch. Pharm. Chem. Life Sci. 338 (2005) 209-216
Archer E., Maigret B., Escrieut C., Pradayrol L., and Fourmy D. Trends Pharmacol. Sci. 24 (2003) 36-40
Hulme E.C., Lu Z.-L., Ward S.D.C., Allman K., and Curtis C.A.M. Eur. J. Pharmacol. 375 (1999) 247-260
Ghanouni P., Steenhuis J.J., Farrens D.L., and Kobilka B.K. Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 5997-6002
Gether U., and Kobilka B.K. J. Biol. Chem. 273 (1998) 17969-17982
Mseeh F., Gerdin M.J., and Dubocovich M.L. Eur. J. Pharmacol. 449 (2002) 29-38
Rees D.C., DeAntonio L., and Eisenberg D. Science 245 (1989) 510-513
Rivara S., Lorenzi S., Mor M., Plazzi P.V., Spadoni G., Bedini A., and Tarzia G. J. Med. Chem. 48 (2005) 4049-4060
Sovová Z., Mazna P., Teisinger J., Štys D., Obšil T., and Ettrich R. Mater. Struct. 11 (2004) 12-14
Kokkola T., Salo O.M.H., Poso A., and Laitinen J.T. J. Pineal Res. 39 (2005) 1-11
Uchikawa O., Fukatsu K., Tokuno R., Kawada M., Matsumoto K., Imai Y., Hinuma S., Kato K., Nishikawa H., Hirai K., Myiamoto M., and Ohkawa S. J. Med. Chem. 45 (2002) 4222-4239
Dubocovich M.L. J. Pharmacol. Exp. Ther. 246 (1988) 902-910
Vakkuri O., Leppäluoto J., and Vuolteenaho O. Acta Endocrinol. 106 (1984) 152-157
Spadoni G., Balsamini C., Diamantini G., Di Giacomo B., and Tarzia G. J. Med. Chem. 40 (1997) 1990-2002
Jellimann C., Mathé-Allainmat M., Andrieux J., Kloubert S., Boutin J.A., Nicolas J.-P., Bennejean C., Delagrange P., and Langlois M. J. Med. Chem. 43 (2000) 4051-4062
Yous S., Andrieux J., Howell H.E., Morgan P.J., Renard P., Pfeiffer B., Lesieur D., and Guardiola-Lemaître B. J. Med. Chem. 35 (1992) 1484-1486
Depreux P., Lesieur D., Ait Mansour H., Morgan P.J., Howell H.E., Renard P., Caignard D.-H., Pfeiffer B., Delagrange P., Guardiola B., Yous S., Demarque A., Adam G., and Andrieux J. J. Med. Chem. 37 (1994) 3231-3239
Mattson R.J., Catt J.D., Keavy D., Sloan C.P., Epperson J., Gao Q., Hodges D.B., Iben L., Mahle C.D., Ryan E., and Yocca F.D. Bioorg. Med. Chem. Lett. 13 (2003) 1199-1202
Epperson J., Deskus J.A., Gentile A.J., Iben L., Ryan E., and Sarbin N.S. Bioorg. Med. Chem. Lett. 14 (2004) 1023-1026
Nathans J., and Hogness D.S. Cell 34 (1983) 807-814
Palczewski K., Kumasaka T., Hori T., Behnke C.A., Motoshima H., Fox B.A., Le Tron I., Teller D.C., Okada T., Stenkamp R.E., Yamamoto M., and Miyano M. Science 289 (2000) 739-745
Petrey D., Xiang Z., Tang C.L., Xie L., Gimpelev M., Mitros T., Soto C.S., Goldsmith-Fischman S., Kernytsky A., Schlessinger A., Koh I.Y.Y., Alexov E., and Honig B. Proteins 53 (2003) 430-435
Okada T., Fujiyoshi Y., Silow M., Navarro J., Landau E.M., and Shichida Y. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 5982-5987
