Crystal Structure of the N-Acetylmannosamine Kinase Domain of GNE

Journal Article · Tue Aug 17 04:00:00 EDT 2010 · PLoS One

DOI:https://doi.org/10.1371/journal.pone.0007165· OSTI ID:1006134

Tong, Yufeng; Tempel, Wolfram; Nedyalkova, Lyudmila; MacKenzie, Farrell; Park, Hee-Won

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 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.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: USDOE
• OSTI ID: 1006134
• Journal Information: PLoS One, Journal Name: PLoS One Journal Issue: (10) ; 10, 2009 Vol. 4
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
BIOSYNTHESIS
CRYSTAL STRUCTURE
DIMERS
DOMAIN STRUCTURE
ENZYMES
MONOMERS
MUTATIONS
PHOSPHOTRANSFERASES
PROTEINS
SIALIC ACID