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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
- 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.
- Subjects :
- Models, Molecular
conformation
Molecular dynamic
obesity
Receptor complex
Magnetic Resonance Spectroscopy
Protein Conformation
Stereochemistry
Conformation analysi
Molecular Sequence Data
Peptide
Biochemistry
Simulated annealing
Molecular dynamics
NMR spectroscopy
Humans
Amino Acid Sequence
Molecular Biology
Protein secondary structure
Root-mean-square deviation
Conformational isomerism
Melanins
chemistry.chemical_classification
Hypothalamic Hormones
Circular Dichroism
Organic Chemistry
Computational Biology
Hydrogen Bonding
Nuclear magnetic resonance spectroscopy
Hormone
MCH
NMR
Pituitary Hormones
Crystallography
chemistry
Solvents
Molecular Medicine
Alpha helix
Subjects
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