Importance of the lactate dehydrogenase quaternary structure in theoretical calculations

Using the example of lactate dehydrogenase, we show that enzyme quaternary structure has an important influence on the structure of the active site and that models that comprise all amino acids in the vicinity of an active site, but are missing this structural information, can lead to incorrect results. We also show that binding isotope effects are very sensitive to the geometric parameters, and thus one should be very cautious when interpreting results obtained with models that are too coarse. In terms of the type of hydrogen bonds, our results indicate that binding isotope effects are pronounced only when a hydrogen bond exhibits some covalent character.