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Conformational features of human melanin-concentrating hormone: an NMR and computational analysis

Conformational features of human melanin-concentrating hormone: an NMR and computational analysis

Authors :
Laura Zaccaro
Benedetto Di Blasio
Carla Isernia
Michele Saviano
Carlo Pedone
Pietro Amodeo
Roberto Fattorusso
Rosa Maria Vitale
Vitale, R. M.
Zaccaro, L
DI BLASIO, B
Fattorusso, R
Isernia, C
Amodeo, P
Pedone, C
Saviano, Michele
Vitale, Rm
Fattorusso, Roberto
Isernia, Carla
Saviano, M.
Source :
ChemBioChem, 4 (2003): 73–81., info:cnr-pdr/source/autori:Vitale, Rosa Maria; Zaccaro, Laura; Di Blasio, Benedetto; Fattorusso, Roberto; Isernia, Carla; Amodeo, Pietro; Pedone, Carlo; Saviano, Michele/titolo:Conformational features of human melanin-concentrating hormone: an NMR and computational analysis/doi:/rivista:ChemBioChem (Print)/anno:2003/pagina_da:73/pagina_a:81/intervallo_pagine:73–81/volume:4
Publication Year :
2003

Abstract

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-Tyr13-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.

Details

Database :
OpenAIRE
Journal :
ChemBioChem, 4 (2003): 73–81., info:cnr-pdr/source/autori:Vitale, Rosa Maria; Zaccaro, Laura; Di Blasio, Benedetto; Fattorusso, Roberto; Isernia, Carla; Amodeo, Pietro; Pedone, Carlo; Saviano, Michele/titolo:Conformational features of human melanin-concentrating hormone: an NMR and computational analysis/doi:/rivista:ChemBioChem (Print)/anno:2003/pagina_da:73/pagina_a:81/intervallo_pagine:73–81/volume:4
Accession number :
edsair.doi.dedup.....7da79eee36e7a30dc3bf8742a3ceff29