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9. In the next lecture, we will learn about the principle of enzyme inhibition as it relates to the development of therapeutics. This question will allow you to fortify your understanding of material from lecture 3 while offering a preview of material to be covered later in the course, a) The crystal structure below shows a moleculo within the active site of a protease enzyme, but interestingly, one of the amino acid residues of the active site has formed a covalent bond with this moleculel Examine the crystal structure carefully and, taking the above into account, name the family of protease (Ser, Thr, Cys. Asp, zinc) this enzyme must belong to. (Note: red = oxygen, blue = nitrogen, yellow = sulfur, lime green - fluorine.) b) Experiments determined that with normal peptide substrates, this enzyme shows a marked preference for cleaving peptide bonds situated between amino acid residues that confer maximum rotational flexibility to the peptide chain. With this data in mind, Indicate on the primary amino acid sequence excerpt shown below where the scissile bond is most likely to lie. No explanation is necessary. (N)-His-Phe-Gly-Gly-Phe-Gln-Leu-Leu-Thr-(C)

C) Provided that the covalent bond formed between the molecule and the enzyme active site residue resulted from Sw2-type displacement of a leaving group, and that no other structural changes occurred, propose a structure for the molecule before it was covalently bound to the active site. Be sure your structure accounts for stereochemistry where necessary. Multiple views are shown below for maximum clarity, and the color scheme Is the same as that given on the previous page. (You may use the generic leaving group "L" in your structure, since its exact identity cannot be deduced from the information given.)