L-Arabinose binding, isomerization, and epimerization by D-xylose isomerase: X-ray/neutron crystallographic and molecular simulation study

Structure. 2014 Sep 2;22(9):1287-1300. doi: 10.1016/j.str.2014.07.002. Epub 2014 Aug 14.


D-xylose isomerase (XI) is capable of sugar isomerization and slow conversion of some monosaccharides into their C2-epimers. We present X-ray and neutron crystallographic studies to locate H and D atoms during the respective isomerization and epimerization of L-arabinose to L-ribulose and L-ribose, respectively. Neutron structures in complex with cyclic and linear L-arabinose have demonstrated that the mechanism of ring-opening is the same as for the reaction with D-xylose. Structural evidence and QM/MM calculations show that in the reactive Michaelis complex L-arabinose is distorted to the high-energy (5)S1 conformation; this may explain the apparent high KM for this sugar. MD-FEP simulations indicate that amino acid substitutions in a hydrophobic pocket near C5 of L-arabinose can enhance sugar binding. L-ribulose and L-ribose were found in furanose forms when bound to XI. We propose that these complexes containing Ni(2+) cofactors are Michaelis-like and the isomerization between these two sugars proceeds via a cis-ene-diol mechanism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aldose-Ketose Isomerases / chemistry*
  • Arabinose / chemistry*
  • Bacterial Proteins / chemistry*
  • Biocatalysis
  • Cadmium / chemistry
  • Crystallography, X-Ray
  • Magnesium / chemistry
  • Molecular Dynamics Simulation
  • Protein Binding
  • Stereoisomerism
  • Streptomyces / enzymology
  • Thermodynamics


  • Bacterial Proteins
  • Cadmium
  • Arabinose
  • Aldose-Ketose Isomerases
  • xylose isomerase
  • Magnesium

Associated data

  • PDB/4QDP
  • PDB/4QDW
  • PDB/4QE1
  • PDB/4QE4
  • PDB/4QE5
  • PDB/4QEE
  • PDB/4QEH