RESUMEN
By molecular mechanics method the conformational properties of two molecules of the tachykinin family, human hemokinin-1 and mouse/rat hemokinin-1, each consisting of 11 amino acids, have been investigated. On the basis of a step-by-step approach we determined the energetically favorable spatial structures of these molecules and their fragments represented as a set of conformations characterized by the relatively labile N-terminal tripeptide and conformationally rigid C-terminal segment. It was shown that conformationally conservative C-terminal octapeptide of the molecules preferably forms two conformations with different structural types of the peptide chain. One of these conformations has an alpha-helical structure, and the other forms the chain's turn that led to an alpha helical turn at the C-terminus. As a result of calculations the energetically favorable ranges of the values of the dihedral angles and orientations of all the residues in low energy conformational states of the molecules were shown. Due to conformational analysis of separate fragments it was possible to trace the process of the second structure formation in these molecules. Based on the results obtained the contribution of inter-residues interaction energy was determined and the role of the each residue in the formation of the optimal spatial structures of hemokinin-1 molecules was estimated.
Asunto(s)
Secuencia Conservada , Fragmentos de Péptidos/química , Taquicininas/química , Secuencia de Aminoácidos , Animales , Humanos , Ratones , Simulación de Dinámica Molecular , Datos de Secuencia Molecular , Pliegue de Proteína , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Ratas , Especificidad de la Especie , TermodinámicaRESUMEN
The conformational features of some glycine-monosubstituted analogues of neurokinins A and B were investigated by the method of theoretical conformational analysis. The calculated geometry and energy parameters permitted one to determine the structural role of each of these substituted amino acids in the mechanism of folding of the low-energy conformational states of neuropeptides. On the basis of the calculated data and the results of biological tests of these analogues, the structure-function relationships of neurokinins A and B were discussed.
Asunto(s)
Sustitución de Aminoácidos , Glicina/química , Modelos Moleculares , Neuroquinina A/química , Neuroquinina B/química , Sustitución de Aminoácidos/genética , Glicina/genética , Neuroquinina A/genética , Neuroquinina B/genética , Estructura Secundaria de Proteína/genéticaRESUMEN
The spatial structure of a neurokinin B molecule was investigated by the method of theoretical conformational analysis. The conformational analysis of this molecule indicated that the possible structure of neurokinin B under polar conditions may be described by five families of low-energy conformations possessing a conformationally relatively rigid C-terminal heptapeptide and variable N-terminal fragments.
Asunto(s)
Modelos Químicos , Neuroquinina A/química , Neuroquinina B/química , Animales , Humanos , Estructura Terciaria de ProteínaRESUMEN
The spatial structure of the neurokinin A molecule was studied by the method of theoretical conformational analysis. On the basis of fragmental analysis, stable structures of the neurokinin A molecule under polar conditions were determined. The structures can be described by four families of low-energy conformations having a relatively labile tripeptide at the C-end and a conformationally rigid heptapeptide at the N-end. It was shown that two of these conformations are virtually isoenergetic structures. One of these is an alpha-helical structure and the other forms two beta-turns at the N-terminus, which change to the turn of the alpha-helix at the C-end.
Asunto(s)
Neuroquinina A/química , Secuencia de Aminoácidos , Modelos Moleculares , Datos de Secuencia Molecular , Neuroquinina B/química , Conformación ProteicaRESUMEN
Conformational properties of five neuropeptides belonging to the calliFMRF-amide series with the Xaa-Pro-Yaa-Gln-Asp-Phe-Met-Arg-Phe-NH2 homologous sequences were studied by the method of theoretical conformational analysis. Three members of these group (1) (Xaa = Thr, Yaa = Gln), (2) (Xaa = Thr, Yaa = Ser), and (3) (Xaa = Yaa = Ser) can stimulate the saliva secretion from the separated salivary gland of the Calliphora vomitoria fly, whereas two other calliFMRF-amides (4) (Xaa = Lys, Yaa = Asn) and (5) (Xaa = Ala, Yaa = Gly) are inactive in this biological test. Low-energy spatial structures of the studied compounds were determined by a conformational analysis. A comparison of the stable structures of the biologically active and inactive neuropeptides revealed a similarity in their conformational properties and allowed determination of the role of separate residues in the peptide folding. The calculations demonstrated that the C-terminal hexapeptide fragment identical in all the five peptides tends to form alpha-helical structure, whereas the variable N-terminal tripeptide regions of CalliFMRF-amides (1)-(5) form more conformationally flexible structures.
Asunto(s)
Modelos Moleculares , Neuropéptidos/química , Amidas/química , Animales , Dípteros/química , Neuropéptidos/farmacología , Fragmentos de Péptidos/química , Conformación Proteica , Pliegue de ProteínaRESUMEN
The spatial structures of human immunoglobulin E pentapeptide Asp-Ser-Asp-Pro-Arg and some of its related peptides were investigated by the method of theoretical conformational analysis. These synthetic peptides have the capacity to inhibit the binding of immunoglobulin E to the mast cells of the skin. The results of the calculations and the data on biological activity of these peptides were used for determination their energy-dependent conformational characteristics that provide their specific interaction with receptors of mast cells.
Asunto(s)
Inmunoglobulina E/química , Oligopéptidos/química , Secuencia de Aminoácidos , Sitios de Unión , Humanos , Inmunoglobulina E/metabolismo , Oligopéptidos/metabolismo , Conformación ProteicaRESUMEN
By conformational analysis and circular dichroism the structure of peptide hormone secretin and its shortened N-terminal fragments in different solvents (water, aqueous solutions of alpha-L-phosphatidic acid and sodium dodecyl sulfate) have been studied. The results obtained by the two methods are compared.
Asunto(s)
Secretina , Dicroismo Circular , Modelos Teóricos , Conformación ProteicaRESUMEN
Theoretical conformational analysis of the octadecapeptide His1-Arg18, corresponding to the entire amino acid sequence of porcine secretin was carried out for a solution of the "direct conformational problem" for this peptide molecule.
Asunto(s)
Arginina , Dipéptidos , Histidina , Secretina , Secuencia de Aminoácidos , Humanos , Conformación Proteica , Secretina/análogos & derivados , Secretina/fisiología , Relación Estructura-ActividadRESUMEN
Spatial structure of peptide hormone secretin was investigated by the theoretical conformational method. A solution of the "direct conformational problem" for this hormone indicated that the possible structure of the secretin molecule under polar conditions may be described only by two families of low-energy conformations, possessing relatively conformational valid (Thr7-Leu22) and variable (His1-Phe6 and Leu23-Val27NH2) fragments. One of these families is comprised by five twists of the alpha-helix, while the second isoenergetic family possesses two short segments of the alpha-helix, divided by an irregular structure of the tetrapeptide.
Asunto(s)
Secretina , Secuencia de Aminoácidos , Humanos , Modelos Biológicos , Oligopéptidos , Conformación Proteica , Secretina/análogos & derivados , Relación Estructura-ActividadRESUMEN
A solution of the "reverse conformational problem" for secretin enables one to predict a series of modified synthetic analogs, the spatial structures of which may assume one of the low-energy states of the native hormone.