Conformational aspects of beta-trypsin interaction with substrates and pancreatic trypsin inhibitor. I. Conformational properties of residues in the enzyme-active center and the structure of a non-valent enzyme-substrate complex

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.     

Study of trypsin-substrate and trypsin-inhibitor complexes. 1. Conformation of Asp-102, His-57 and Ser-195 residues in the trypsin active center

Using the semi-empirical method of conformational analysis low energetic conformations were found for trypsin's catalytic triad Asp102, His57, Ser195 in the field of the active centre that consisted of about 800 atoms. It was shown that within the enzyme structure conformations which are preferential for isolated residues are formed. Lability obtained for the side chains is in accord with their functions in enzymatic catalysis. Results of the calculations carried out correlate with the X-ray data for trypsin complexes.     

Conformation of glycopeptides with L- and D-stereoisomers of Ala and Glu amino acids

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.     

Structural organization of [met]enkephalin and endorphin molecules. II. Theoretical conformation analysis of alpha-, gamma- and delta-endorphins]

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.     

Structural organization of [Met]enkephalin and endorphin molecules. I. Theoretical conformation analysis of [Met]enkephalin

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.     

Calculation of the structure of the serotonin-antibiotic lasalocid A complex by conformation analysis and the Monte Carlo method

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.     

Small-angle diffuse x-ray scattering on fine muscle filaments

Theoretical small-angle diffuse scattering curves from muscle thin filament models have been calculated. The curves reveal a maximum at 115' scattering angle. It has been shown that the maximum is due to the pitch of F-actin helix. Theoretical curves are in good agreement with the earlier obtained curves of small-angle diffuse scattering from F-actin dilute solutions.     

Conformational aspects of beta-trypsin interaction with substrates and pancreatic trypsin inhibitor. III. Catalytic act of trypsin and its inhibition

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.