Question

The side chain of ________ has a pKa in the physiological pH range and is therefore often involved in proton transfer during enzymatic catalysis.

Answer 1

The side chain of Histidine of all amino acids has a pKa in the physiological pH range. It is one of the essential amino acids, which means we, humans can’t synthesize it.

It contains imidazole side chain. Which plays crucial role in proton transfer reactions.

The imidazole is a common coordinating ligand in metalloproteins e.g. haemoglobin, myoglobin and cytochromes. And also a part of catalytic sites in certain enzymes. Often the basic nitrogen of histidine is used to abstract a proton from serine, threonine, or cysteine to activate it as a nucleophile.

Histidine is used to quickly shuttle protons in a histidine proton shuttle. It can do this by abstracting a proton with its basic nitrogen to make a positively charged intermediate and then use another molecule, a buffer, to extract the proton from its acidic nitrogen.

In carbonic anhydrases, a histidine proton shuttle is utilized to rapidly shuttle protons away from a zinc-bound water molecule to quickly regenerate the active form of the enzyme.

Histidine is also important in haemoglobin in helices E and F. Histidine assists in stabilising oxyhaemoglobin and destabilising CO-bound haemoglobin.