Structural and biochemical characterization of a trapped coenzyme a adduct of Caenorhabditis elegans glucosamine-6-phosphate N-acetyltransferase 1

Helge C. Dorfmueller (Lead / Corresponding author), Wenxia Fang, Francesco V. Rao, David E. Blair, Helen Attrill, Daan M. F. van Aalten

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    12 Citations (Scopus)

    Abstract

    Glucosamine-6-phosphate N-acetyltransferase 1 (GNA1) produces GlcNAc-6-phosphate from GlcN-6-phosphate and acetyl coenzyme A. Early mercury-labelling experiments implicated a conserved cysteine in the reaction mechanism, whereas recent structural data appear to support a mechanism in which this cysteine plays no role. Here, two crystal structures of Caenorhabditis elegans GNA1 are reported, revealing an unusual covalent complex between this cysteine and the coenzyme A product. Mass-spectrometric and reduction studies showed that this inactive covalent complex can be reactivated through reduction, yet mutagenesis of the cysteine supports a previously reported bi-bi mechanism. The data unify the apparently contradictory earlier reports on the role of a cysteine in the GNA1 active site.
    Original languageEnglish
    Pages (from-to)1019-1029
    Number of pages11
    JournalActa Crystallographica Section D: Biological Crystallography
    Volume68
    Issue number8
    DOIs
    Publication statusPublished - 2012

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