The GlcNAc-PI de-N-acetylase: structure, function, and activity

TY - JOUR

T1 - The GlcNAc-PI de-N-acetylase

T2 - structure, function, and activity

AU - Urbaniak, Michael D.

AU - Ferguson, Michael A. J.

N1 - Copyright 2010 Elsevier B.V., All rights reserved. Chapter 3 in issue "Glycosylphosphatidylinositol (GPI) anchoring of proteins"

PY - 2009

Y1 - 2009

N2 - The N-acetylglucosamine phosphatidylinositol (GlcNAc-PI) de-. N-acetylase catalyzes the removal of the N-acetyl group from GlcNAc-PI in the second step of GPI biosynthesis. The GlcNAc-PI de-. N-acetylase is a 252-residue integral membrane protein containing a single N-terminal membrane spanning domain, with the majority of the protein on the cytoplasmic face of the ER. Site-directed mutagenesis studies have lead to the proposal of a zinc-dependent mechanism of action analogous to zinc peptidases. The activity of the GlcNAc-PI de-. N-acetylase can be measured both in vivo and in vitro, and active recombinant protein has been obtained. The enzyme is a potential drug target for the treatment of African sleeping sickness, and differences in substrate recognition and channeling between mammalian and trypanosomal enzymes have been exploited to produce species-specific inhibitors.

AB - The N-acetylglucosamine phosphatidylinositol (GlcNAc-PI) de-. N-acetylase catalyzes the removal of the N-acetyl group from GlcNAc-PI in the second step of GPI biosynthesis. The GlcNAc-PI de-. N-acetylase is a 252-residue integral membrane protein containing a single N-terminal membrane spanning domain, with the majority of the protein on the cytoplasmic face of the ER. Site-directed mutagenesis studies have lead to the proposal of a zinc-dependent mechanism of action analogous to zinc peptidases. The activity of the GlcNAc-PI de-. N-acetylase can be measured both in vivo and in vitro, and active recombinant protein has been obtained. The enzyme is a potential drug target for the treatment of African sleeping sickness, and differences in substrate recognition and channeling between mammalian and trypanosomal enzymes have been exploited to produce species-specific inhibitors.

UR - https://www.scopus.com/pages/publications/77954838969

U2 - 10.1016/S1874-6047(09)26003-3

DO - 10.1016/S1874-6047(09)26003-3

M3 - Article

AN - SCOPUS:77954838969

SN - 1874-6047

VL - 26

SP - 49

EP - 64

JO - Enzymes

JF - Enzymes

ER -