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Molecular mechanics simulations of a conformational rearrangement of D ‐xylose in the active site of D ‐xylose isomerase
Author(s) -
Smart Oliver S.,
Akins John,
Blow David M.
Publication year - 1992
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.340130203
Subject(s) - xylose isomerase , chemistry , isomerase , substrate (aquarium) , isomerization , activation energy , steric effects , stereochemistry , conformational change , ring (chemistry) , ligand (biochemistry) , enzyme , biochemistry , catalysis , organic chemistry , receptor , oceanography , geology
A proposed reaction mechanism for the enzyme D ‐xylose isomerase involves the ring opening of the cyclic substrate with a subsequent conformational rearrangement to an extended open‐chain form. Restrained energy minimization was used to simulate the rearrangement. In the ring‐opening step, the substrate energy function was gradually altered from a cyclic to an open‐chain form, with energy minimization after each change. The protein/sugar contact energy did not increase significantly during the process, showing that there was no steric hindrance to ring opening. The conformational rearrangement involves an alteration in the coordination of the substrate to metal ion [1], which was induced by gradually changing restraints on metal/ligand distances. By allowing varying amounts of flexibility in the protein and examining a simplified model system, the interactions of the sugar with metal ion [1] and its immediate ligands were found to be the most important contributors to the energy barrier for the change. Only small changes in the positions of protein atoms were required. The energy barrier to the rearrangement was estimated to be less than the Arrhenius activation energy for the enzymatic reaction. This is in accordance with experimental indications that the isomerization step is rate determining. © 1992 Wiley‐Liss, Inc.