The GlcNAc-PI de-N-acetylase

structure, function, and activity

Michael D. Urbaniak, Michael A. J. Ferguson

    Research output: Contribution to journalArticle

    2 Citations (Scopus)

    Abstract

    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.
    Original languageEnglish
    Pages (from-to)49-64
    Number of pages16
    JournalEnzymes
    Volume26
    DOIs
    Publication statusPublished - 2009

    Fingerprint

    N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase
    Acetylesterase
    Zinc
    African Trypanosomiasis
    Mutagenesis
    Biosynthesis
    Enzymes
    Site-Directed Mutagenesis
    Recombinant Proteins
    Membrane Proteins
    Peptide Hydrolases
    N-acetylglucosaminylphosphatidylinositol
    Membranes

    Cite this

    @article{b5ef4ef3a8f44c4197d86c9d17e0743e,
    title = "The GlcNAc-PI de-N-acetylase: structure, function, and activity",
    abstract = "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.",
    author = "Urbaniak, {Michael D.} and Ferguson, {Michael A. J.}",
    note = "Copyright 2010 Elsevier B.V., All rights reserved. Chapter 3 in issue {"}Glycosylphosphatidylinositol (GPI) anchoring of proteins{"}",
    year = "2009",
    doi = "10.1016/S1874-6047(09)26003-3",
    language = "English",
    volume = "26",
    pages = "49--64",
    journal = "Enzymes",
    issn = "1874-6047",
    publisher = "Academic Press Inc.",

    }

    The GlcNAc-PI de-N-acetylase : structure, function, and activity. / Urbaniak, Michael D.; Ferguson, Michael A. J.

    In: Enzymes, Vol. 26, 2009, p. 49-64.

    Research output: Contribution to journalArticle

    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 - http://www.scopus.com/inward/record.url?scp=77954838969&partnerID=8YFLogxK

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

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

    M3 - Article

    VL - 26

    SP - 49

    EP - 64

    JO - Enzymes

    JF - Enzymes

    SN - 1874-6047

    ER -