ANION BINDING AT THE ACTIVE-SITE OF TRYPANOSOMAL TRIOSEPHOSPHATE ISOMERASE - MONOHYDROGEN PHOSPHATE DOES NOT MIMIC SULFATE

The three-dimensional structure of triosephosphate isomerase complexed with the competitive inhibitor HPO4(2-) was determined by X-ray crystallography to a resolution of 0.24 nm. A comparison with the native crystal structure, where SO4(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.