Question

7. The HIV protease structure was solved very early in the process of developing anti-HIV drugs. Importantly, the protease was found to be quite similar to proteases like chymotrypsin and trypsin. Compare and contrast the catalytic mechanism and binding properties of chymotrypsin, trypsin, and the HIV protease. Catalitic mechanism chymotryps in this enzyme help digest and works in the intestine to help Break down Large protein molecules

Answer 1

7. Chymotrypsin is a proteolytic enzyme acting on the digestive system of many organisms. It facilitates cleavage of the peptide bonds by a hydrolysis reaction, which despite being thermodynamically favourable, occurs extremely slowly in the absence of a catalyst. The main substrates of chymotrypsin are peptide bonds in which amino acid N-terminal to the bond is a tryptophan, tyrosine, phenylalanine or leucine. Chymotrypsin cleaves peptide bonds by attacking the unreactive carbonyl group with a powerful nucleophile, serine 195 residue located at the active site of the enzyme, which briefly becomes covalently bounded to the substrate, forming an enzyme-substrate intermediate. Along with histidine 57 and aspartic acid 102, the serine residue constitutes the catalytic triad of the active site.

Trypsin breaks down peptides using a hydrolysis reaction into amino acid building blocks. The active site is composed of three catalytic residues serine 195, histidine 57 and aspartate 102. Serine is bonded to the imidazole ring of histidine. When histidine accepts a proton from serine an alkoxide nucleophile is formed. This nucleophile attacks the substrate when the substrate is present. The role of aspartate is to hold the histidine in proper position making it a good proton acceptor. It involves two tetrahedral intermediates and an Acyl-enzyme intermediate.

HIV protease catalyzes hydrolysis in a concerted manner. The nucleophilic water molecule and the protonated Asp25 simultaneously attack the scissile peptide bond during catalysis.