hiv protease uses aspartate side chains at its active site.
hiv protease uses aspartate side chains at its active site.
hiv protease uses _ side chains at its active site?
aspartate
nelfinavir is a protease inhibitor: it inhibits hiv-1 and hiv-2 proteases. hiv protease is an aspartate protease which splits viral protein molecules into smaller fragments, and it is vital to both the replication of the virus within the cell, and also to the release of mature viral particles from an infected cell. nelfinavir is a competitive inhibitor (2 nm) which is designed to bind tightly and is not cleaved due to the presence of a hydroxyl group as opposed to a keto group in the middle amino acid residue mimic, which would be otherwise s-phenylcysteine. all protease inhibitors bind to the protease, the precise mode of binding determines how the molecule inhibits the protease. the way nelfinavir binds the enzyme may be sufficiently unique to reduce cross-resistance between it and other pis. also, not all pis inhibit both hiv-1 and hiv-2 proteases.
nelfinavir
mutations that code for alterations of the conformational shape facilitate resistance of hiv to protease inhibitors. the locations of these mutations are primarily in the active site of the hiv protease enzyme as well as outside of the active site, including those at protease cleavage sites in the gag-pol polyprotein precursors. the cleavage sites have highly diverse sequences, so the protease recognizes its substrates not based on sequence but rather the conserved 3d shape the substrates share when bound at the active site. this conserved shape has been named the " substrate envelope". the active site mutations have been shown to directly change the interactions of the inhibitors, and mostly occur at positions where inhibitors contact protease residues beyond the substrate envelope. the non-active site mutations are considered to affect by other mechanisms, like influencing dimer stability and conformational flexibility.
discovery and development of hiv-protease inhibitors