Paper Citing NAMD - Abstract
Langan, Paul; Sangha, Amandeep K.; Wymore, Troy; Parks, Jerry M.; Yang, Zamin Koo; Hanson, B. Leif; Fisher, Zoe; Mason, Sax A.; Blakeley, Matthew P.; Forsyth, V. Trevor; Glusker, Jenny P.; Carrell, Horace L.; Smith, Jeremy C.; Keen, David A.; Graham, David E.; Kovalevsky, Andrey
L-Arabinose Binding, Isomerization, and Epimerization by D-Xylose Isomerase: X-Ray/Neutron Crystallographic and Molecular Simulation Study
STRUCTURE, 22:1287-1300, SEP 2 2014
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 S-5(1) 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 Ni2+ cofactors are Michaelis-like and the isomerization between these two sugars proceeds via a cis-ene-diol mechanism.
