"Polypeptides can be cleaved either chemically or enzymatically. Enzymes that catalyse

the hydrolytic cleavage of peptide bonds are called proteases. Proteases fall into four main

mechanistic classes: serine, cysteine, aspartyl and metalloproteases. In the active sites of

serine and cysteine proteases, the eponymous residue $($for which the enzyme is named$)$ is

usually paired with a proton$-$withdrawing group to promote nucleophilic attack on the

peptide bond. Aspartyl proteases and metalloproteases activate a water molecule to serve

as the nucleophile, rather than using a functional group of the enzyme itself. However, the

overall process of peptide bond scission is essentially the same for all protease classes."

Nature $459,371-378(21$ May $2009)$

"The mechanism of cysteine proteases $($Seen in the image$)$ is similar to that of serine

proteases in the use of a strong nucleophile and the formation of a covalent enzyme$-$

substrate complex. However, the nucleophile is the sulphur atom of a cysteine residue, as

opposed to the oxygen atom of a serine. In the cysteine protease papain, the backbone $NH$

groups of cysteine $25$ and glutamine $19$ form the oxyanion hole." Nature $459,371-378/21$

May $2009)$

Explain how $pH$ will affect the efficiency of this enzyme. How $Km$ and $K_{\text{c}\text{a}\text{t}}$ will change as

$pH$ increases from $2$ to $12?(10$ pts$)$