AUTHOR=Ogata Makoto , Fukamizo Tamo , Ohnuma Takayuki 

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

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.654706

DOI=10.3389/fmolb.2021.654706

ISSN=2296-889X

ABSTRACT=<p>4-<italic>O</italic>-<italic>β</italic>-tri-<italic>N</italic>-acetylchitotriosyl moranoline (GN<sub>3</sub>M) 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 GN<sub>3</sub>M to HEWL and revealed that the binding is driven by a favorable enthalpy change (Δ<italic>H</italic>° = −11.0 kcal/mol) with an entropic penalty (−<italic>T</italic>Δ<italic>S</italic>° = 2.6 kcal/mol), resulting in a free energy change (Δ<italic>G</italic>°) of −8.4 kcal/mol [<xref ref-type="bibr" rid="B16">Ogata et al. (2013)</xref> 288, 6,072–6,082]. Dissection of the entropic term showed that a favorable solvation entropy change (−<italic>T</italic>Δ<italic>S</italic><sub>solv</sub>° = −9.2 kcal/mol) is its sole contributor. The change in heat capacity (Δ<italic>C</italic><sub>p</sub>°) for the binding of GN<sub>3</sub>M 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 GN<sub>3</sub>M and HEWL.</p>