Functional anion binding sites in dogfish M4 lactate dehydrogenase

X-ray diffraction data have been collected from dogfish M₄ lactate dehydrogenase crystals in which ammonium sulfate had been exchanged by citrate at pH 6.0 and 7.8. Data were also collected from crystals which had been soaked in 0.1 m oxamate, a lactate dehydrogenase inhibitor. The difference electron density maps obtained have been interpreted in terms of two exchangeable anion binding sites, one at the active center and one between two subunits. The active center site is coincident with the substrate binding site in a ternary complex, while the subunit boundary site, which has been observed in several different forms of the enzyme, may be involved in stabilizing the tetramer.