Question

HMG-CoA reductase, a critical enzyme in cholesterol synthesis is the target or statin inhibitors. You are characterizing a possible new inhibitor and want to determine its mode of binding to HMG-CoA reductase. Equilibrium dialysis measurements at 25 C, 30°C, and 37 C yielded dissociation constants (K.) of 2.5 x 10" М, 1.5 x 10", and 1.0 x 103 M, respectively, for the HMG-CoA reductase-inhibitor complex. a. Is the binding becoming better or worse with increasing temperature? Explain. b. Using Excel or similar program, tabulate the data, make a van't Hoff plot, and use itto determine ΑΔΙΙ" and Δ1S®. for the dissociation reaction. c. What are the corresponding AAH and AAS for complex formation? d. What is ΔGo, for complex formation at 25° C? e. Is this inhbitor binding driven by entropy or enthalpy? Explain. f. What mode of binding (i.e., forces or interactions) would you predict for the inhibitor? What's your rationale?

Answer 1

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