Mechanisms of EX‡ stabilization 5: Covalent Catalysis •…

Mechanisms of EX‡ stabilization 5: Covalent Catalysis • Covalent catalysis use used by many proteases to hydrolyze the peptide bonds in protein substrates. – Serine Proteases: use deprotonated serine R-O- as the nucleophile – Cysteine Proteases use deprotonated cysteine R-S- as the nucleophile • These attack peptide bonds (amides), converting them to the more reactive ester. • The ester or thioester is formed between the enzyme and the substrate as an acyl enzyme intermediate. • This acyl enzyme intermediate is then attacked by water.