2CH5

Crystal structure of human N-acetylglucosamine kinase in complex with N-acetylglucosamine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.199 
  • R-Value Work: 0.167 
  • R-Value Observed: 0.167 

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Ligand Structure Quality Assessment 


This is version 2.0 of the entry. See complete history


Literature

Structures of Human N-Acetylglucosamine Kinase in Two Complexes with N-Acetylglucosamine and with Adp/Glucose: Insights Into Substrate Specificity and Regulation.

Weihofen, W.A.Berger, M.Chen, H.Saenger, W.Hinderlich, S.

(2006) J Mol Biol 364: 388

  • DOI: https://doi.org/10.1016/j.jmb.2006.08.085
  • Primary Citation of Related Structures:  
    2CH5, 2CH6

  • PubMed Abstract: 

    N-Acetylglucosamine (GlcNAc), a major component of complex carbohydrates, is synthesized de novo or salvaged from lysosomally degraded glycoconjugates and from nutritional sources. The salvage pathway requires that GlcNAc kinase converts GlcNAc to GlcNAc-6-phosphate, a component utilized in UDP-GlcNAc biosynthesis or energy metabolism. GlcNAc kinase belongs to the sugar kinase/Hsp70/actin superfamily that catalyze phosphoryl transfer from ATP to their respective substrates, and in most cases catalysis is associated with a large conformational change in which the N-terminal small and C-terminal large domains enclose the substrates. Here we report two crystal structures of homodimeric human GlcNAc kinase, one in complex with GlcNAc and the other in complex with ADP and glucose. The active site of GlcNAc kinase is located in a deep cleft between the two domains of the V-shaped monomer. The enzyme adopts a "closed" configuration in the GlcNAc-bound complex and GlcNAc interacts with residues of both domains. In addition, the N-acetyl methyl group contacts residues of the other monomer in the homodimer, a unique feature compared to other members of the sugar kinase/Hsp70/actin superfamily. This contrasts an "open" configuration in the ADP/glucose-bound structure, where glucose cannot form these interactions, explaining its low binding affinity for GlcNAc kinase. Our results support functional implications derived from apo crystal structures of GlcNAc kinases from Chromobacter violaceum and Porphyromonas gingivalis and show that Tyr205, which is phosphorylated in thrombin-activated platelets, lines the GlcNAc binding pocket. This suggests that phosphorylation of Tyr205 may modulate GlcNAc kinase activity and/or specificity.


  • Organizational Affiliation

    Freie Universität Berlin, Institut für Chemie und Biochemie-Kristallographie, Takustrasse 6, 14195 Berlin-Dahlem, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
NAGK PROTEIN
A, B, C, D
347Homo sapiensMutation(s): 0 
EC: 2.7.1.59
UniProt & NIH Common Fund Data Resources
Find proteins for Q9UJ70 (Homo sapiens)
Explore Q9UJ70 
Go to UniProtKB:  Q9UJ70
PHAROS:  Q9UJ70
GTEx:  ENSG00000124357 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9UJ70
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NDG
Query on NDG

Download Ideal Coordinates CCD File 
K [auth D]2-acetamido-2-deoxy-alpha-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-PVFLNQBWSA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
E [auth A],
G [auth B],
I [auth C]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
F [auth A],
H [auth B],
J [auth C],
L [auth D],
M [auth D]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.199 
  • R-Value Work: 0.167 
  • R-Value Observed: 0.167 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.537α = 63.43
b = 98.482β = 75.66
c = 101.981γ = 75.06
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-09-18
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Refinement description, Version format compliance
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Other, Structure summary