Phosphatidylinositol glycan anchor biosynthesis class W (PIGW) (PIGW)

Phosphatidylinositol glycan anchor biosynthesis class W (PIGW) is an integral membrane protein located in the endoplasmic reticulum that functions as a GPI-anchored protein biosynthetic palmitoyltransferase. It catalyzes the third step of glycosylphosphatidylinositol (GPI) anchor biosynthesis, specifically the acylation of the inositol ring of glucosaminyl-phosphatidylinositol (GlcN-PI) using palmitoyl-CoA as the acyl donor (UniProt: Q5VYS4; PubMed: 15618512). This modification is a prerequisite for the subsequent addition of mannose residues and the eventual attachment of the GPI anchor to the C-terminus of precursor proteins. In humans, biallelic mutations in the PIGW gene lead to Hyperphosphatasia with mental retardation syndrome 5 (HPMRS5), a condition characterized by intellectual disability, seizures, and elevated serum alkaline phosphatase (PubMed: 24443451). While human PIGW is primarily of interest in the context of genetic disorders, its fungal ortholog, Gwt1, is a validated target for novel antifungal agents. Drugs such as manogepix selectively inhibit the fungal enzyme to disrupt cell wall integrity and fungal growth, representing a significant therapeutic strategy for resistant fungal infections (PubMed: 29339583).

Other names

GPI-inositol palmitoyltransferasePhosphatidylinositol-glycan biosynthesis class W proteinPIG-WGPI-anchored protein biosynthetic palmitoyltransferaseGwt1 (fungal ortholog)

Inhibition of the inositol acyltransferase enzyme, which prevents the palmitoylation of glucosaminyl-phosphatidylinositol (GlcN-PI), thereby halting the assembly of glycosylphosphatidylinositol (GPI) anchors.