title: Biochemical characterization of human and murine isoforms of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE).
abstract: The bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme for the biosynthesis of sialic acids, terminal components of glycoconjugates associated with a variety of physiological and pathological processes. Different protein isoforms of human and mouse GNE, deriving from splice variants, were predicted recently: GNE1 represents the GNE protein described in several studies before, GNE2 and GNE3 are proteins with extended and deleted N-termini, respectively. hGNE2, recombinantly expressed in insect and mamalian cells, displayed selective reduction of UDP-GlcNAc 2-epimerase activity by the loss of its tetrameric state, which is essential for full enzyme activity. hGNE3, which had to be expressed in Escherichia coli, only possessed kinase activity, whereas mGNE1 and mGNE2 showed no significant differences. Our data therefore suggest a role of GNE1 in basic supply of cells with sialic acids, whereas GNE2 and GNE3 may have a function in fine-tuning of the sialic acid pathway.
authors.affiliation: Institute of Biochemistry and Molecular Biology, Charité-University Medicine Berlin, Campus Benjamin Franklin, Arnimallee 22, 14195, Berlin-Dahlem, Germany.
authors.forename: Stefan O
authors.initials: SO
authors.lastname: Reinke
authors.forename: Colin
authors.initials: C
authors.lastname: Eidenschink
authors.forename: Chris M
authors.initials: CM
authors.lastname: Jay
authors.forename: Stephan
authors.initials: S
authors.lastname: Hinderlich
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D009097:Multienzyme Complexes; D011994:Recombinant Proteins; C482901:UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase