RESUMEN
The spatial structure of cardioactive Thr-Pro-Ala-Glu-Asp-Phe-Met-Arg-Phe-NH2 molecule has been investigated using a theoretical conformational analysis. The low-energy conformations of the molecule were found, the values of the backbone and side T-T chain dihedral angles of amino acid residues constituting the peptide were determined, and the energies of intra- and interresidual interactions were estimated. It is revealed that the spatial structure of this molecule can exist in 11 stable backbone forms.
Asunto(s)
Aminoácidos/química , FMRFamida/química , Precursores de Proteínas/química , Modelos Moleculares , Conformación Proteica , 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
Theoretical conformational analysis was used to study the spatial structure and conformational properties of myelopeptides, bone marrow peptide mediators. The low-energy conformations of myelopeptides MP-4 (Phe-Arg-Pro-Arg-Ile-Met-Thr-Pro), MP-5 (Val-Val-Tyr-Pro-Asp), and MP-6 (Val-Asp-Pro-Pro) were found; the values of dihedral angles of backbone and side chains of the amino acid residues were determined; and the energies of intra- and interresidual interactions were estimated.
Asunto(s)
Oligopéptidos/química , Secuencia de Aminoácidos , Modelos Moleculares , Datos de Secuencia Molecular , Conformación Proteica , TermodinámicaRESUMEN
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
The spatial organization and conformational flexibility of neuropeptides of the gallatostatin family was studied by the method of theoretical conformational analysis. It was found that the spatial organization of neuropeptides allows the realization of folded helical structures of the C-terminal pentapeptide, and the flexibility of neuropeptides is due to a great number of low-energy states in the N-terminal fragment of the molecule.
Asunto(s)
Neuropéptidos/química , Secuencia de Aminoácidos , Enlace de Hidrógeno , Modelos Moleculares , Datos de Secuencia Molecular , Estructura Secundaria de Proteína , TermodinámicaRESUMEN
Theoretical conformational analysis was used to study the spatial structure and conformational properties of myelopeptides, bone-marrow peptide mediators. The low-energy conformations of three hexapeptides MP-1 (Phe-Leu-Gly-Phe-Pro-Thr), MP-2 (Leu-Val-Val-Tyr-Pro-Trp), and MP-3 (Leu-Val-Cys-Tyr-Pro-Gln) were found, the values of dihedral angles of the backbone and side chains of the amino acid residues constituting these peptides were determined, and the energies of intra- and interresidual interactions were estimated.
Asunto(s)
Modelos Moleculares , Oligopéptidos/química , Secuencia de Aminoácidos , Animales , Humanos , Conformación Molecular , TermodinámicaRESUMEN
The spatial and electronic structures of kiotorphin and its biologically active analogue [D-Arg2]-kiotorphin were studied. It was shown that [D-Arg2]-kiotorphin has a more rigid structure compared with the native molecule. The D-izomerization of arginine restricts the conformational mobility of the main chain of the molecule, which completely rules out its unfolded form. The electronic characteristics of the molecule in this case substantially change.
Asunto(s)
Endorfinas/química , Modelos Moleculares , Conformación ProteicaRESUMEN
The comparative study of the spatial organization and conformational properties of NmU-8 neuropeptide and its modified analogs with available experimental data has been carried out. The effect of amino acids point mutation on conformational states of native neuropeptide has been discussed. The low-energy conformations responsible for neuropeptide contractile activity was revealed.
Asunto(s)
Neuropéptidos/química , Modelos Moleculares , Neuropéptidos/genética , Mutación Puntual , 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
Conformational energy calculations were carried out for beta-endorphin. Its spatial structure can be described by nine low-energy conformations. The calculations yielded the values of all dihedral angles of the backbone and side chains of these forms as well as intra- and inter-residue interaction energies.
Asunto(s)
Encefalina Metionina/análisis , betaendorfina/análisis , Secuencia de Aminoácidos , Datos de Secuencia Molecular , Conformación ProteicaRESUMEN
Conformational energy calculations were carried out for neuropeptides alpha-, gamma- and delta-endorphins, which are 1-16, 1-17 and 1-19 fragments respectively, of beta-endorphin. The proposed computational scheme yielded all possible low-energy conformational sets for these hormones. Specific features of spatial organization of each compound and similarities of their structures are discussed.
Asunto(s)
Endorfinas/análisis , Encefalina Metionina/análisis , Secuencia de Aminoácidos , Datos de Secuencia Molecular , Fragmentos de Péptidos/análisis , Conformación Proteica , alfa-Endorfina , gamma-EndorfinaRESUMEN
Using a semi-empirical method, an a priori conformational analysis of the [Met]-enkephalin molecule was carried out. Calculations yielded the values of all dihedral angles of the backbone and side chains of the peptide's forms as well as intra- and inter-residue interaction energies.
Asunto(s)
Endorfinas/análisis , Encefalina Metionina/análisis , Matemática , Modelos Químicos , Conformación ProteicaRESUMEN
The conformational aspects of interaction of the antibiotic X537A at complexation with serotonin, hydration of molecules and their complex were studied by the methods of theoretical conformational analysis and Monte-Carlo.
Asunto(s)
Lasalocido , Serotonina , Sustancias Macromoleculares , Conformación Molecular , Método de MontecarloRESUMEN
Using conformational analysis spatial structure and conformational properties of the N-terminal tridecapeptide--endorphine molecules were investigated. Calculations were based on the fragmental analysis using non-valent, electrostatic, torsional interactions and hydrogen bonds. It was shown that tridecapeptide could exist in several low-energetical conformational states. Enkephaline fragments structure depends on the most perspective structure of free metioninenkephaline. The results can be used for conformational analysis of endorphine molecules, for structure--function relations study.
Asunto(s)
Endorfinas , Péptidos , Oligopéptidos , Conformación Proteica , betaendorfinaRESUMEN
Theoretical conformational analysis of the tetrahedral complexes of trypsin with the N-acetyl-L-lysine methyl amide, which are formed at the acylation and the deacylation stages of the catalytical act has been carried out. The lowest energy conformations are shown to be productive ones. All favorable structures of N-acetyl-L-lysyl-trypsin and N-acetyl-L-arginyl-trypsin acylenzymes have been analysed. The global conformations of both complexes are found to be very similar with the structures providing for a transition to the second tetrahedral state. Conformations of the nonbonded, tetrahedral and acyl complexes with N-acetyl-L-lysine methyl amide are compared and the differences in orientation of atomic groups participating in the catalysis are revealed. All changes of optimal structures of the complexes indispensable for the catalytical process are shown to proceed in a spontaneous way without introduction of any intramolecular strain.
Asunto(s)
Inhibidor de Tripsina Pancreática de Kazal , Inhibidores de Tripsina , Tripsina , Acetilación , Secuencia de Aminoácidos , Animales , Bovinos , Modelos Moleculares , Oligopéptidos , Conformación Proteica , Especificidad por SustratoRESUMEN
Basing on the results of the theoretical conformational analysis of the nonbonded and valence complexes of trypsin with substrate molecules, the catalytical act of the enzyme is described in details as a spontaneous process. Conformational aspects of interactions of trypsin with pancreatic trypsin inhibitor are analysed. The complete inhibition process and the geometry of the enzyme-inhibitor complex are described in details. The point amino acid replacements, which will provide for an exclusion of BPTI inhibition and will radically change the specificity of the enzyme are proposed.
Asunto(s)
Inhibidor de Tripsina Pancreática de Kazal/metabolismo , Inhibidores de Tripsina/metabolismo , Tripsina/metabolismo , Secuencia de Aminoácidos , Animales , Sitios de Unión , Catálisis , Bovinos , Quimotripsina/metabolismo , Modelos Moleculares , Conformación Proteica , Especificidad por SustratoRESUMEN
The theoretical conformational analysis of potential surfaces of Ser-195, His-57, Asp-102 and Gln-192 side chains in the active center of native beta-trypsin has been carried out. The above residues are shown to exist in low-energy conformational states in the free enzyme and in its nonbonded substrate complexes. Interrelations between the flexibility of the residues and their catalytical functions were revealed. Conformational aspects of interaction of trypsin with N-acetyl-L-lysine and N-acetyl-L-alanyl--L-alanyl--L-lysyl--L-alanyl methyl amide and with the Gly-12--Ile-19 BPTI fragment were analysed. The productive binding of the substrate at the nonbonded complex stage is shown to take place exclusively in the lowest energy conformation of the enzyme-substrate complex. Basing on theoretical and experimental evidence, the problems of primary and secondary specificity of trypsin, and potential properties of the native protein to form a productive nonbonded complex and to react at the subsequent stages of the catalytical act are discussed. Conformational changes in the active center and interactions with a substrate are shown to result from stabilizing enzyme-substrate interactions. Trypsin inhibition by BPTI molecule does not take place at the nonbonded complex stage.
Asunto(s)
Inhibidor de Tripsina Pancreática de Kazal/metabolismo , Inhibidores de Tripsina/metabolismo , Tripsina/metabolismo , Secuencia de Aminoácidos , Animales , Sitios de Unión , Bovinos , Fenómenos Químicos , Química , Técnicas In Vitro , Modelos Moleculares , Conformación ProteicaRESUMEN
On the base of the semi-empirical method of conformational analysis low-energetic conformations have been found for the glycopeptides with the O-beta-N-acetyl-D-muramic acid or the O-beta-N-acetyl--D-glucosaminyl-(1-4)-N-acetyl-D-muramic acid in the glycan part and L-Ala--D-GluNH2, L-Ala--L-GluNH2, D-Ala--D-GluNH2 in the peptide part. It was shown that for either molecule preferentiability of any conformation is determined mainly by interactions between dipeptide and muramic acid residue.