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Conformational Features of Human Melanin‐Concentrating Hormone: An NMR and Computational Analysis
Author(s) -
Vitale Rosa Maria,
Zaccaro Laura,
Di Blasio Benedetto,
Fattorusso Roberto,
Isernia Carla,
Amodeo Pietro,
Pedone Carlo,
Saviano Michele
Publication year - 2003
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200390017
Subject(s) - conformational isomerism , chemistry , nuclear magnetic resonance spectroscopy , protein secondary structure , molecular dynamics , crystallography , stereochemistry , molecule , computational chemistry , biochemistry , organic chemistry
The conformational features of human melanin‐concentrating hormone (hMCH) [Asp1‐Phe2‐Asp3‐Met4‐Leu5‐Arg6‐cyclo(SS)(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 α 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.