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Figure 1. The HIV life cycle. The HIV enter a cell (bind to it and inject their genes into the interior), copy their genes and proteins (by cooptin g the cell's machinery and raw material), and pack the fresh copies into new vir al particles able to spread to and infect other cells. The viral components invo lved in any of those steps can serve as targets for drugs. In particular the pro tease involved in step 8 (blue pacman--like object, the mouth being the active s ite, see Fig. 2).
(Reproduced by kind permission from Quade Paul, Echo Medical Media).
Figure 2. The HIV--1--Protease is a dimeric protein, formed by two identical chains. (left) A tube model representation of the three--dimensional n ative (folded) structure of the HIV--1--Protease in complexation with a traditio nal (active site centerred) inhibitor (yellow). This enzyme is an homodimer, tha t is a protein formed by two identical polypeptide chains each (monomer) contain ing 99 amino acids. Also shown is a schematic pacman--like structure which relat es to Fig. 1 (see step 8). Mutation of the HIV expressing the protease can induce changes in the shape of the active site (mouth of pacman) making the inhibitor non--effective, without much reducing the enzymatic activity. (right) The folding of the dimer takes place in three steps in which the first t wo correspond to the independent folding of the monomers and the third to the di merization. In the figure a snapshot of a numerical simulation of the dimer in p resence of 3 p--LES is given. The LES are indicated as thick coloured tubes, whi le the p-LES (non--conventional inhibitor) are highlighted in terms of segments of thin yellow tubes. p--LES prevent the monomers to form the folding nucleus an d thus to reach the native conformation and form the active site.
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