Thermodynamic Analysis for Binding of 4-O-β-tri-N-acetylchitotriosyl Moranoline, a Transition State Analogue Inhibitor for Hen Egg White Lysozyme.

ABSTRACT: 4-O-β-tri-N-acetylchitotriosyl moranoline (GN₃M) is a transition-state analogue for hen egg white lysozyme (HEWL) and identified as the most potent inhibitor till date. Isothermal titration calorimetry experiments provided the thermodynamic parameters for binding of GN₃M to HEWL and revealed that the binding is driven by a favorable enthalpy change (ΔH° = -11.0 kcal/mol) with an entropic penalty (-TΔS° = 2.6 kcal/mol), resulting in a free energy change (ΔG°) of -8.4 kcal/mol [Ogata et al. (2013) 288, 6,072-6,082]. Dissection of the entropic term showed that a favorable solvation entropy change (-TΔS _solv° = -9.2 kcal/mol) is its sole contributor. The change in heat capacity (ΔC _p°) for the binding of GN₃M was determined to be -120.2 cal/K·mol. These results indicate that the bound water molecules play a crucial role in the tight interaction between GN₃M and HEWL.

SUBMITTER: Ogata M 

PROVIDER: S-EPMC8222817 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature