Crystal Structure of Triosephosphate Isomerase Complexed with 2-Phosphoglycolate at 0.83-Å Resolution*

The atomic resolution structure ofLeishmania mexicana triosephosphate isomerase complexed with 2-phosphoglycolate shows that this transition state analogue is bound in two conformations. Also for the side chain of the catalytic glutamate, Glu167, two conformations are observed. In both conformations, a very short hydrogen bond exists between the carboxylate group of the ligand and the catalytic glutamate. The distance between O11 of PGA and Oε2 of Glu167 is 2.61 and 2.55 Å for the major and minor conformations, respectively. In either conformation, Oε1 of Glu167 is hydrogen-bonded to a water network connecting the side chain with bulk solvent. This network also occurs in two mutually exclusive arrangements. Despite the structural disorder in the active site, the C termini of the β strands that construct the active site display the least anisotropy compared with the rest of the protein. The loops following these β strands display various degrees of anisotropy, with the tip of the dimer interface loop 3 having very low anisotropy and the C-terminal region of the active site loop 6 having the highest anisotropy. The pyrrolidine ring of Pro168 at the N-terminal region of loop 6 is in a strained planar conformation to facilitate loop opening and product release.