What would happen in a histidine residue was used as an acid

What would happen in a histidine residue was used as an acid catalyst? What would happen as pH increases?

Solution

Histidine is an amino acid present at many enzyme active sites.It contains two nitrogen atomson the imidazole ring that can function with an unique characteristic of acid-base catalyst. It is is often the residue involved in these acid/base reactions, since it has a pKa close to neutral pH and can therefore both accept and donate protons. As the proton transfer step determines the rate of the reaction, it is vital to examine the effectiveness of the general catalysis.

General acid - partial transfer of a proton from Histidine lowers the free energy of the transition state and consequently the rate of reaction decreases with increase in pH. Specific acid - protonation lowers the free energy of the transition state, rate of reaction decreases with increase in pH. The pH dependence is usually due to the side groups of the amino acids. A change in pH changes the protonation pattern and can, in extreme cases, result in protein denaturation which may be the cause.