Isochorismate pyruvate lyase

Isochorismate Pyruvate LyaseIsochorismate Pyruvate Lyase

Gateway for Substrate Entry and Product Exit

Significance of the Isochorismate Isochorismate is the end product of the shikimate pathway that is essential for the synthesis of many primary and secondary metabolites. It is synthesized from chorismate by isochorismate synthase enzyme. Chorismate is the common precursor for synthesis of aromatic amino acids, cofactors, phenazines and siderophores. Many enzymes are involved in the pathway and these enzymes are present in microbes and plants and absent in mammals and provide potential targets for antimicrobial drugs and herbicides.Isochorismate pyruvate Lyase (IPL) is one such enzyme.

FunctionFunction

It is involved in the catalysis of the transformation of isochorismate to pyruvate and salicylate. This reaction is the committed step in the biosynthesis of salicylate-based siderophores in several pathogenic bacteria. In plants, salicylate produced from isochorismate is important for the plant defense mechanisms known as local and systemic acquired resistance It has also been found to have secondary activity of catalyzing the transformation of chorismate to prephenate (chorismate mutase activity), although this is weak. The physiological role of IPL uses a pericyclic hydrogen transfer mechanism to produce salicylate from isochorismate as opposed to the notion that general base or acid catalysis would occur. This property resembles chorismate mutase enzyme that catalyze pericyclic reactions. IPL is a structural homolog of chorismate mutase despite very low sequence identity (approx 20%). The similarity is restricted to the active sites which are conserved (Annu. Rev. Biophys. 2008. 37:153–73) and it has been found that chorismate mutase cannot be mutated to acquire IPL activity. IPL has been considered for improvement of its secondary activity computationally using hybrid quantum mechanics/ Molecular mechanics (J. AM. CHEM. SOC. 2008, 130, 2894-2895).