Question

A bioinformatics study revealed that the enzymes called vasoinhibins have a Cys–His–Ser catalytic triad. These enzymes regulate angiogenesis (the formation of new blood vessels) and are thus potential drug targets for cancer treatment. If the cysteine residue serves as the nucleophile, what are the possible roles of histidine and serine in enzyme catalysis?

Answer 1

Catalytic triad includes a group of three well coordinated amino acids namely cysteine, histidine and serine. They are present at the active site of hydrolyses and transferase enzyme. These catalytic triad carries out covalent catalysis with the help of a nucleophile. These residues polarise and activate the nucleophile and increases its reactivity in order to attack the substrate. This leads to formation of a covalent intermediate which undergoes hydrolysis. The hydrolysis causes the release of the product and form free enzyme.

Vasoinhibin is an endothelial protease which uses cysteine as a nucleophile. The serine residue is used to orient the histidine in the triad. If cysteine residue serves as a nucleophile then the Histidine residue will help the orientation of serine residue such that it under goes nucleophilic attack through the process of catalysis. The serine residue consist of a hydroxyl group that attacks carbonyl carbon present on the peptide bond of the substrate. Whereas, the histidine coordinates with the serine residue to carry out an attack on the substrate as it takes the hydrogen from serine's hydroxyl group and break the peptide bond on the substrate and regenerating free enzyme. TheHistidine has the ability to accept a proton. Any single change in the amino acid may cause complete loss of the function of enzyme.