Interaction of chlorpromazine with myoglobin and hemoglobin: A comparative study
TL;DR: Thermodynamic analysis revealed that binding of CPZ to hemoglobin was exothermic, whereas binding to myoglobin was endothermic with a high entropic contribution, suggesting that CPZ binding toMyoglobin is hydrophobic in nature.
Abstract: The mode and nature of the binding of chlorpromazine (CPZ), a psychotropic drug, with myoglobin, a monomeric muscle protein, were studied spectrofluorometrically and the results compared with those from the binding of CPZ to hemoglobin, a tetrameric allosteric protein from red blood cells (RBC). CPZ interacted with myoglobin in a non-cooperative mode, with a binding constant of 8.4 × 103 M−1 in 0.145 M NaCl, pH 6.8, whereas in the case of hemoglobin this interaction was found to be positively cooperative with a binding constant of 4.2 × 103M−1. The interaction of CPZ with myoglobin was not influenced by the NaCl molarity of the solution, whereas CPZ interaction with hemoglobin significantly decreased with increasing NaCl molarity, indicating that CPZ-hemoglobin binding is mostly electrostatic in nature, whereas that of the CPZ-myoglobin complex is of a non-electrostatic type. Thermodynamic analysis revealed that binding of CPZ to hemoglobin was exothermic (ΔH° = − 2.65 kcal/mol), whereas binding to myoglobin was endothermic (ΔH° = + 1.39 kcal/mol) with a high entropic contribution (ΔS° = + 23 cal/degree/mol), suggesting that CPZ binding to myoglobin is hydrophobic in nature. Such contrasting binding features of this drug have been discussed in the light of a typical subunit interaction property present and absent in hemoglobin and myoglobin, respectively.
Cites background from "Interaction of chlorpromazine with ..."
...A single-site protein, such as myoglobin, cannot accomplish this sort of communication, as one myoglobin molecule is completely independent of the state of the other and thus the interaction of phenothiazines with myoglobin is found to be non-cooperative in nature (Bhattacharyya et al., 1994)....
...Such interaction is found to be cooperative in nature (Bhattacharyya et al., 1990, 1994)....
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