Question

You are studying a cysteine protease and want to better understand its mechanism and inhibition.

1. What are the likely consequences of mutating the active site cysteine to an alanine and why?
2. What are the likely consequences of mutating the active site cysteine to a serine and why?
3. What considerations should you make when designing a competitive inhibitor for your protease and why?

Answer 1

• Mutating cysteine to alanine-the active aite containing cysteine has role in breaking peptide bond between two amino acid by deprotonation reaction by cysteine amino acid.but if alanine is introduced instead of cystein leads to changing of catalaytic site of cystein protease.because alanine has no polar functional group to carry out hydrolysis of peptide bond.
• Mutating cysteine serine- serine is the polar amino acid so it can forms hydrogen bonds with target amino acid chain but dont have capasity to break peptide bond.
• While deaighning compititor inhibitor for cysteine protease i ll take care of addition of compititor having structure of small peptide to break into 2 separate amino acids.so inhibitor should mimic the structure like target of protease.