Anion binding at the active site of trypanosomal triosephosphate isomerase. Monohydrogen phosphate does not mimic sulphate.
The three-dimensional structure of triosephosphate isomerase complexed with the competitive inhibitor SO-4(2) was determined by X-ray crystallography to a resolution of 0.24 nm. A comparison with the native crystal structure, where SO-4(2) is bound, revealed five changes: (a) a 0.10-nm shift of the anion-binding site; (b) a further closing of the flexible loop of the enzyme; (c) a 'swinging in' of the side chain of the catalytic Glu, that is chi 1 changes from (+) to (-) synclinal; (d) an altered water structure; (e) a disappearance of the conformational heterogeneity at the C-terminus of strand beta 7. Some of these changes may be related to the different hydrogen-bond pattern about the two different anions. However, the distance of 0.10 nm between the sulphur and phosphorus positions is unexpected and remains intriguing.
Verlinde
C L
CL
BIOSON Research Institute, University of Groningen, The Netherlands.
Noble
M E
ME
Kalk
K H
KH
Groendijk
H
H
Wierenga
R K
RK
Hol
W G
WG
D000818:Animals; D000838:Anions / Q000378:metabolism*; D001665:Binding Sites; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000378:metabolism; D013464:Sulfuric Acids / Q000378:metabolism; D014305:Triose-Phosphate Isomerase / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000201:enzymology*; D014961:X-Ray Diffraction
D000838:Anions; D009943:Organophosphorus Compounds; D013464:Sulfuric Acids; D014305:Triose-Phosphate Isomerase