3EO3

Crystal structure of the N-acetylmannosamine kinase domain of human GNE protein


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.84 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.207 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

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

Tong, Y.Tempel, W.Nedyalkova, L.Mackenzie, F.Park, H.W.

(2009) PLoS One 4: e7165-e7165

  • DOI: https://doi.org/10.1371/journal.pone.0007165
  • Primary Citation of Related Structures:  
    3EO3

  • PubMed Abstract: 

    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. This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.


  • Organizational Affiliation

    Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
A, B, C
333Homo sapiensMutation(s): 0 
Gene Names: GNEGLCNE
EC: 5.1.3.14 (PDB Primary Data), 2.7.1.60 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for Q9Y223 (Homo sapiens)
Explore Q9Y223 
Go to UniProtKB:  Q9Y223
PHAROS:  Q9Y223
GTEx:  ENSG00000159921 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9Y223
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

Unit Cell:
Length ( Å )Angle ( ˚ )
a = 127.946α = 90
b = 127.946β = 90
c = 127.247γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
SOLVEphasing
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data scaling

Structure Validation

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Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2008-10-07
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Refinement description, Version format compliance
  • Version 1.2: 2017-10-25
    Changes: Refinement description
  • Version 1.3: 2024-02-21
    Changes: Data collection, Database references, Derived calculations