Three-dimensional model of aspartic protease from human endogenous retrovirus

The aspartic protease of human endogenous retrovirus HERV-K plays an essent ial role in its life cycle. Besides its main function of processing the HER V-K polyprotein, this enzyme also can process the polyprotein of HIV-1. To analyze the structural bases of the specificity of HERV-K aspartic protease , a three-dimensional model of this enzyme was build basing on the homology to known structures of aspartic proteases from other retroviruses. The mod el was compared with the X-ray structure of HIV-1 protease with substrate-b ased inhibitor. The major attention was given to the analysis of difference s and similarities of the binding pockets. The amino acid residues responsi ble for the specificity of subsites, were identified. An attempt was made t o give a structural explanation to the resistance of the enzyme to some cli nically used inhibitors of HIV-1 protease.