York, D.M., Darden, T.A., Pedersen, L.G., (1993) J. Chem. Phys., 99, pp. 8345-8348
Laskowski, R.A., MacArthur, M.W., Moss, D.S., Thornton, J.M., (1993) J. Appl. Cryst., 26, pp. 283-291
The conformational features of human melanin-concentrating hormone (hMCH) [Asp1-Phe2-Asp3-Met4-Leu5-Arg6-cyclo(S[bond]S)(Cys7-Met8-Leu9-Gly10-Arg11-Val12-T yr13-Arg14-Pro15-Cys16)-Trp17-Gln18-Val19], in water and in a CD(3)CN/H(2)O (1:1 v/v) mixture at 298 K, have been determined by NMR spectroscopy followed by simulated annealing and molecular dynamics analyses to identify conformer populations. Backbone clustering analysis of NMR-spectroscopy-derived structures in the 7-16 peptide region led to the identification of a single representative structure in each solvent. Both root mean square deviation clustering and secondary structure analysis of the final conformers in both solvents show substantial convergence of most conformers into a single fold in the 4-17 region, with a limited variability around Gly10 and Tyr13 on going from CD(3)CN/H(2)O to pure water. The main feature deduced from the analysis of secondary structures is the occurrence of an N-terminal alpha helix of variable length, which spans an overall residue range of 2-9. A comparative analysis in the two solvents highlights that these structures are substantially different from that reported in the literature for the cyclic MCH(5-14) subunit of salmon MCH, which was used to perform a molecular characterization of the MCH/receptor complex. Our conformational data call for a critical revision of the proposed MCH/receptor complex model.
271 Records (256 escludendo Abstract e Conferenze). Impact factor totale: 1112.593 (1050.995 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 1170.907 (1107.143 escludendo Abstract e Conferenze).