Figure 1.

A representation of the catalytic side chains at the active site of TIM (PDB ID: 1NEY), using the numbering of the residues from the wild-type TIM from Saccharomyces cerevisiae.^15,19,20 The substrate dihydroxyacetone phosphate (DHAP) is deprotonated by the carboxylate side chain of E165.^21,22 The neutral imidazole side chain of H95 is positioned to stabilize negative charge that develops at O-1 or O-2 of the isomeric enediolate phosphate reaction intermediates,^23,24 and the amide side chain of N10 is positioned to stabilize negative charge that develops at O-1.²⁵ The alkyl ammonium cation side chain of K12 interacts with both the phosphodianion and the negatively charged oxygen of an enediolate phosphate reaction intermediate.²⁶⁻²⁹