Crystal structure of the N-acetylmannosamine kinase domain of GNE.

Crystal structure of the N-acetylmannosamine kinase domain of GNE.

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UDP-GlcNAc 2-epimerase/ManNAc 6-kinase, GNE, is a bi-functional enzyme that plays a key role in sialic acid biosynthesis.Mutations of the GNE protein cause sialurea or autosomal recessive inclusion body myopathy/Nonaka myopathy.GNE is the only human protein that contains a kinase domain belonging to the STRONTIUM SUPPORT II ROK (repressor, ORF, kinase) family.We solved the structure of the GNE kinase domain in the ligand-free state.The protein exists predominantly as a dimer in solution, with small populations of monomer and higher-order oligomer in equilibrium with the dimer.

Crystal packing analysis reveals the existence of a crystallographic hexamer, and that the kinase domain dimerizes through the C-lobe subdomain.Mapping of disease-related missense mutations onto the kinase domain structure revealed that the mutation sites could be classified into four different groups based on the location - dimer interface, interlobar helices, protein surface, or within other secondary structural elements.The crystal structure of the kinase domain of GNE provides a structural basis for understanding disease-causing mutations and a model of hexameric wild type full length enzyme.This article can also be viewed as an enhanced version in which the text of the article is integrated Hoodies/Fleece with interactive 3D representations and animated transitions.Please note that a web plugin is required to access this enhanced functionality.

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