Molecular mechanisms underlying the recognition of the mRNA 5' terminal structure called "cap" by the eukaryotic initiation factor 4E (eIF4E) are crucial for cap-dependent translation. To gain a deeper insight into how the yeast eIF4E interacts with the cap structure, isothermal titration calorimetry and the van't Hoff analysis based on intrinsic protein fluorescence quenching upon titration with a series of chemical cap analogs were performed, providing a consistent thermodynamic description of the binding process in solution. Equilibrium association constants together with thermodynamic parameters revealed similarities and differences between yeast and mammalian eIF4Es. The yeast eIF4E complex formation was enthalpy-driven and entropy-opposed for each cap analog at 293 K. A nontrivial isothermal enthalpy-entropy compensation was found, described by a compensation temperature, T-c = 411 +/- 18 K. For a low affinity analog, 7-methylguanosine monophosphate, a heat capacity change was detected, Delta C-p degrees = +5.2 +/- 1.3 kJ.mol(-1).K-1. The charge-related interactions involving the 5'-5' triphosphate bridge of the cap and basic amino acid side chains at the yeast eIF4E cap-binding site were significantly weaker (by Delta Delta H degrees(vH) of about +10 kJ.mol(-1)) than those for the mammalian homologues, suggesting their optimization during the evolution.