Structural features of the inactive and active states of the melanin-concentrating hormone receptors: Insights from molecular simulations (573 views)
Proteins (ISSN: 0887-3585, 1097-0134, 1097-0134electronic), 2004 Sep 15; 56(3): 430-448.
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Paper type: Journal Article,
Impact factor: 4.429, 5-year impact factor: 2.964
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-3142779088&partnerID=40&md5=554eb0ed57423f730a793fd97109ec66
Keywords: Comparative Molecular Dynamics, Gpcrs, Inactive And Active States, Mchrs, Hormone Receptor, Melanin Concentrating Hormone, Melanin Concentrating Hormone Receptor, Receptor Blocking Agent, Unclassified Drug, Amino Acid Sequence, Article, Complex Formation, Conformational Transition, Hormone Receptor Interaction, Molecular Model, Priority Journal, Protein Conformation, Amino Acid Motifs, Binding Sites, Biphenyl Compounds, Chemistry, Physical, Computer Simulation, Hydrogen Bonding, Hypothalamic Hormones, Ligands, Chemical, Molecular Sequence Data, Naphthalenes, Peptide Fragments, Pituitary Hormones, Protein Structure, Secondary, G-Protein-Coupled, Somatostatin, Rhodopsin, Sequence Deletion, Sequence Homology, Thermodynamics,
Affiliations:
*** IBB - CNR ***
Department of Chemistry, Univ. of Modena and Reggio Emilia, Modena, Italy
Ist. di Biostrutture/Bioimmagini CNR, Napoli, Italy
Dulbecco Telethon Institute, Department of Chemistry, Univ. of Modena and Reggio Emilia, Modena, Italy
References:
Not available.
Proteins (ISSN: 0887-3585, 1097-0134, 1097-0134electronic), 2004 Sep 15; 56(3): 430-448.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 4.429, 5-year impact factor: 2.964
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-3142779088&partnerID=40&md5=554eb0ed57423f730a793fd97109ec66
Keywords: Comparative Molecular Dynamics, Gpcrs, Inactive And Active States, Mchrs, Hormone Receptor, Melanin Concentrating Hormone, Melanin Concentrating Hormone Receptor, Receptor Blocking Agent, Unclassified Drug, Amino Acid Sequence, Article, Complex Formation, Conformational Transition, Hormone Receptor Interaction, Molecular Model, Priority Journal, Protein Conformation, Amino Acid Motifs, Binding Sites, Biphenyl Compounds, Chemistry, Physical, Computer Simulation, Hydrogen Bonding, Hypothalamic Hormones, Ligands, Chemical, Molecular Sequence Data, Naphthalenes, Peptide Fragments, Pituitary Hormones, Protein Structure, Secondary, G-Protein-Coupled, Somatostatin, Rhodopsin, Sequence Deletion, Sequence Homology, Thermodynamics,
Affiliations:
*** IBB - CNR ***
Department of Chemistry, Univ. of Modena and Reggio Emilia, Modena, Italy
Ist. di Biostrutture/Bioimmagini CNR, Napoli, Italy
Dulbecco Telethon Institute, Department of Chemistry, Univ. of Modena and Reggio Emilia, Modena, Italy
References:
Not available.
Structural features of the inactive and active states of the melanin-concentrating hormone receptors: Insights from molecular simulations
Comparative molecular dynamics simulations of both subtypes 1 and 2 of the melanin-concentrating hormone receptor (MCHR1 and MCHR2, respectively) in their free and hormone-bound forms have been carried out. The hormone has been used in its full-length and truncated forms, as well as in 16 mutated forms. Moreover, MCHR1 has been simulated in complex with T-226296, a novel orally active and selective antagonist. The comparative analysis of an extended number of receptor configurations suggests that the differences between inactive (i.e., free and antagonist-bound) and active (i.e., agonist-bound) states of MCHRs involve the receptor portions close to the E/DRY and NPxxY motifs, with prominence to the cytosolic extensions of helices 2, 3, 6, and 7. In fact, the active forms of these receptors share the release of selected intramolecular interactions found in the inactive forms, such as that between R3.50 of the E/DRY motif and D2.40, and that between Y7.53 of the NPxxY motif and F7.60. Another feature of the active forms of both MCHRs is the approach of "helix 8" to the cytosolic extension of helix 3. These features of the active forms are concurrent with the opening of a cleft at the cytosolic end of the helix bundle. For both MCHRs, the agonist-induced chemical information transfer from the extracellular to the cytosolic domains is mediated by a cluster of aromatic amino acids in helix 6, following the ligand interaction with selected amino acids in the extracellular half of the receptor. (C) 2004 Wiley-Liss, Inc.
Comparative molecular dynamics simulations of both subtypes 1 and 2 of the melanin-concentrating hormone receptor (MCHR1 and MCHR2, respectively) in their free and hormone-bound forms have been carried out. The hormone has been used in its full-length and truncated forms, as well as in 16 mutated forms. Moreover, MCHR1 has been simulated in complex with T-226296, a novel orally active and selective antagonist. The comparative analysis of an extended number of receptor configurations suggests that the differences between inactive (i.e., free and antagonist-bound) and active (i.e., agonist-bound) states of MCHRs involve the receptor portions close to the E/DRY and NPxxY motifs, with prominence to the cytosolic extensions of helices 2, 3, 6, and 7. In fact, the active forms of these receptors share the release of selected intramolecular interactions found in the inactive forms, such as that between R3.50 of the E/DRY motif and D2.40, and that between Y7.53 of the NPxxY motif and F7.60. Another feature of the active forms of both MCHRs is the approach of "helix 8" to the cytosolic extension of helix 3. These features of the active forms are concurrent with the opening of a cleft at the cytosolic end of the helix bundle. For both MCHRs, the agonist-induced chemical information transfer from the extracellular to the cytosolic domains is mediated by a cluster of aromatic amino acids in helix 6, following the ligand interaction with selected amino acids in the extracellular half of the receptor. (C) 2004 Wiley-Liss, Inc.
Structural features of the inactive and active states of the melanin-concentrating hormone receptors: Insights from molecular simulations
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Structural features of the inactive and active states of the melanin-concentrating hormone receptors: Insights from molecular simulations
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Vitale RM, Zaccaro L, Di Blasio B, Fattorusso R, Isernia C, Amodeo P, Pedone C, Saviano M
* Conformational features of human melanin-concentrating hormone: an NMR and computational analysis (490 views)
Chembiochem (ISSN: 1439-4227, 1439-7633, 1439-4227linking), 2014 Sep 17; 4(1): 73-81.
Impact Factor: 3.088
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* Conformational features of human melanin-concentrating hormone: an NMR and computational analysis (490 views)
Chembiochem (ISSN: 1439-4227, 1439-7633, 1439-4227linking), 2014 Sep 17; 4(1): 73-81.
Impact Factor: 3.088
View Export to BibTeX Export to EndNote
1 Records (1 excluding Abstracts).
Total impact factor: 3.088 (3.088 excluding Abstracts).
Total 5 year impact factor: 3.162 (3.162 excluding Abstracts).
Total impact factor: 3.088 (3.088 excluding Abstracts).
Total 5 year impact factor: 3.162 (3.162 excluding Abstracts).
573 views. Last view on Thursday 16 November 2023, 4:09:37
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