Indole-3-glycerol-phosphate synthase (IGPS)

Indole-3-glycerol-phosphate synthase (IGPS) is an enzyme (EC 4.1.1.48) that catalyzes the formation of indole-3-glycerol phosphate from 1-(2-carboxyphenylamino)-1-deoxy-D-ribulose 5-phosphate in the biosynthetic pathway for aromatic amino acids, specifically tryptophan, phenylalanine, and tyrosine. IGPS belongs to the lyase family, more specifically carboxy-lyases, and is structurally organized as a (β/α)_8_ barrel protein. The enzyme is present in bacteria, fungi, and plants, with functional differences in its domain organization (multifunctional in some species). In plants, IGPS is also involved at a metabolic branchpoint for secondary metabolites such as benzoxazinoids that serve as defense compounds. IGPS has been investigated as a potential antimicrobial drug target due to its essential role in tryptophan biosynthesis in bacteria and pathogens such as Mycobacterium tuberculosis, whereas in humans, tryptophan is acquired through diet and biosynthetic targeting poses less risk. No clinically approved drugs currently target IGPS, but it remains of pharmacological interest in infectious disease. Structural and mechanistic studies on IGPS help guide inhibitor design and its application in antimicrobial development.

Other names

indoleglycerol phosphate synthetaseindoleglycerol phosphate synthaseindole-3-glycerophosphate synthase1-(2-carboxyphenylamino)-1-deoxy-D-ribulose-5-phosphate carboxy-lyase (cyclizing 1-C-(indol-3-yl)glycerol-3-phosphate-forming)carboxy-lyase (cyclizing)

Enzyme inhibition: Drugs would act as inhibitors of IGPS, blocking the formation of indole-3-glycerol phosphate and thereby shutting down tryptophan biosynthesis in target microorganisms