Mechanism of action of aspartic proteinases. V. Conformational characteristics of fragments of substrate-binding sites in rhizopuspepsin and HIV-1 proteinase

The conformational states of side chains of catalytic Asp residues in active sites of HIV-1 protease and rhizopuspepsin in the potential field of free enzymes were studied by using theoretical conformational analysis. Structural factors that stabilize the conformation of these residues in free enzymes were revealed. Methods of molecular mechanics were used to estimate the stabilization energy of the Met46-Phe53 labile fragments of HIV-1 protease in the potential field of their nearest surrounding amino acid residues for the conformations characteristic of the free protein and similar to that of the protein in enzyme-inhibitor complexes. In solution, the conformational state of the fragments of the free enzyme was concluded to be similar to that observed in the enzyme complex with the ligand and different from that determined by X-ray diffraction analysis. This difference was ascribed to the effect of crystal packing.