PCL102H1 Lecture Notes - Lecture 19: Hiv-1 Protease, X-Ray Crystallography, Drug Design

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Lecture 19 protein structure and raional drug design. Protein funcion is determined by the 3-d shape; shape is determined by primary amino acid sequence (usually. Protein folding into higher structures take few seconds. Essenial step: growing a crystal of pure protein in soluion. Small amount of very concentrated protein in soluion, separate into droplets. Let each crystal dry slowly, precise condiions (ph, temp) are diferent for each protein. Crystals (very hard to grow) take months or years to grow, they contain precisely stacked molecules of proteins. Proteins that are usually found in membranes are greasy (hydrophobic), don"t go into soluion well. Hiv virus life cycle: hiv proteins, encoded by hiv genome, play a big role in the hiv life cycle. Protein of interest (15) of the hiv virus, since most drugs target proteins. Need 2 protease molecules to form acive enzyme. Need to cut the natural substrate into 2 pieces, to take out the iniial lead compound.

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