Thermodynamic studies of the interaction of trp aporepressor with tryptophan analogs.

The association of L-tryptophan and some of its analogs, including three conformationally restricted analogs, with trp aporepressor (apo trpR) was studied by isothermal titration microcalorimetry. Contributions of the functional groups of a ligand to the free energy change, delta G degrees', and enthalpy change, delta H degree', of the interaction were evaluated on a molecular basis. Analogs without the alpha-amino group (i.e. desamino analogs) bind with a slightly higher affinity to the protein. On the other hand, descarboxy analogs show weaker binding to the apo trpR. In addition, it is found that there exists enthalpy-entropy compensation for the association of the congener series of ligands with the protein. The entropy change, delta S degree', appears to play a more important role in the binding of the conformationally restricted analogs than in the binding of L-tryptophan and the unlocked ligands.