Oct 24, 2024 · Cryo-EM structures reveal how the first-in-class antifungal drug manogepix inhibits fungal GWT1, a key enzyme for GPI-anchored protein synthesis.

Molecules inhibiting N -acetylglucosaminyl-phosphatidylinositol de- N -acetylase (GlcNAc-PI de- N -acetylase, PIGL/GPI12) or the inositol acyltransferase (GWT1), central for glycosylphosphatidylinositol (GPI) biosynthesis, halt the growth of intraerythrocytic asexual parasites during the trophozoite stages of the intraerythrocytic developmental ...

May 1, 2019 · The yeast Gwt1 protein, which is an acyltransferase, catalyzes the acylation of the inositol moiety of GPI on the endoplasmic reticulum membrane (Jigami, 2008; Umemura et al., 2003), and is essential for the biosynthesis of GPI anchors.

To date, two novel targets in the GPI biosynthetic pathway, Gwt1 and Mcd4 have been exploited for the development of antifungal inhibitors. Gwt1 catalyzes inositol acylation whereas Mcd4 catalyzes phosphoethanolamine addition to first mannose.

Jun 27, 2003 · The incorporation of inositol into GPI-anchored proteins was reduced in gwt1 mutant, indicating involvement of GWT1 in GPI biosynthesis. We analyzed the early steps of GPI biosynthesis in vitro by using membranes prepared from gwt1 and Deltagwt1 cells.

Gwt1 is a catalytic inositol acyltransferase that transfers fatty acyl chains to the inositol fraction of GPI precursors. Gwt1 plays a crucial role in maintaining fungal cell wall integrity and enabling cell adhesion to mucosal surfaces.

Oct 17, 2022 · Glycosylphosphatidylinositol (GPI) is a conserved post-translational modification to anchor cell surface proteins to plasma membrane in eukaryotes. GWT1 is involved in GPI anchor biosynthesis; it is required for inositol acylation in yeast.

Jun 22, 2012 · Gwt1 is a promising antifungal drug target, and gepanacin is a useful probe for studying how disrupting GPI-anchor synthesis impairs viability and alters host–pathogen interactions in genetically intractable fungi.

Dec 12, 2014 · Utilizing a chemical genomics-based screening platform referred to as the Candida albicans fitness test (CaFT), we have identified novel inhibitors of Gwt1 and a second enzyme in the glycosylphosphatidylinositol (GPI) cell wall anchor pathway, Mcd4.

Jun 27, 2003 · The incorporation of inositol into GPI-anchored proteins was reduced in gwt1 mutant, indicating involvement of GWT1 in GPI biosynthesis. We analyzed the early steps of GPI biosynthesis in vitro by using membranes prepared from gwt1 and Δ gwt1 cells.