HIV and Hepatitis C HCV protease cleavage prediction

As previously described in Chapter 2, viral protease is one of the enzymes typically accompanying HIV RNA and HCV into the cell (see Figure 2.10, Chapter 2). It cleaves the precursor viral polyproteins (the substrate) at specific cleavage-recognition sites when they emerge from the ribo-somes of the host cell as one long sequence (Figure 6.3(a)). When certain substrate configurations occur (a certain sequence of amino acids), the protease cleaves the viral polyprotein at a specific point in the substrate (Figure 6.3(b)). Conventionally, the polyprotein substrate is labelled with unique P identifiers (one for each amino acid) and the protease region around the active site with unique S identifiers (Figure 6.3(c)).

This cleavage step is essential in the final maturation step of HIV and HCV. That is, protease is responsible for the post-translation processing

3 Available from http://www.rulequest.com.

4 Available from http://www.salford-systems.com/.

5 Available from http://www.sgi.com/tech/mlc/index.html.

Helper T cell ribosome HIV polyprotein

Helper T cell ribosome HIV polyprotein

Protease

Protease

aal aa2 aa3 aa4 aa5 aa6 aa7 aa8

Protease active site aal aa2 aa3 aa4 aa5 aa6 aa7 aa8

Protease active site

Protease

Polyprotein substrate

Protease

Rest of protease t

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