Thermodynamics of phospholipase A2-ligand interactions.

Future investigations into the role of the structure of phospholipid substrates and the interrelationships between substrate, calcium, and enzyme conformation in the activation process are clearly needed. Enzyme dimerization in the activation of phospholipase A2 has been indicated, and a complex equilibrium between calcium, substrate, and monomer and dimer enzyme apparently exists. The incorporation of proton binding further complicates the scheme, and one is quickly faced with obtaining a large number of equilibrium constants in order to describe the system explicitly. Nevertheless, similarly complex systems have been well characterized using thermodynamic approaches such as those described herein. An excellent example is the complex equilibrium involving the protonation of the histidine residues and the binding of a mononucleotide to ribonuclease A. Achieving a complete thermodynamic description of that system allowed the investigators to make strong mechanistic statements about models for the catalytic mechanism of ribonuclease A. Since phospholipase A2 is available for study at the same level of detail, one can anticipate a similar degree of quantitative detail regarding the important interactions of this enzyme to be forthcoming.