A Comparative Interaction between Copper Ions with Alzheimer's ß Amyloid Peptide and Human Serum Albumin.

The interaction of Cu(2+) with the first 16 residues of the Alzheimer's amyliod ß peptide, Aß(1-16), and human serum albumin (HSA) were studied in vitro by isothermal titration calorimetry at pH 7.2 and 310 K in aqueous solution. The solvation parameters recovered from the extended solvation model indicate that HSA is involved in the transport of copper ion. Complexes between Aß(1-16) and copper ions have been proposed to be an aberrant interaction in the development of Alzheimer's disease, where Cu(2+) is involved in Aß(1-16) aggregation. The indexes of stability indicate that HSA removed Cu(2+) from Aß(1-16), rapidly, decreased Cu-induced aggregation of Aß(1-16), and reduced the toxicity of Aß(1-16) + Cu(2+) significantly.

Polymyxins interaction to the human serum albumin: A thermodynamic and computational study.

Polymyxin B and E (colistin), are a group of cationic charged cyclic antibiotic lipopeptides that are frequently used in the clinics to treat infections caused by the multidrug-resistant gram-negative bacteria. Since the interactions with the blood plasma drug-transport proteins may play a critical role in determining their pharmacological and pharmacokinetic profiles, we studied the binding properties of polymyxins to the human serum albumin (HSA) under simulated physiological conditions by the combination of biophysical approaches, such as isothermal titration calorimetry (ITC), fluorescence anisotropy, circular dichroism (CD) buttressed by computational studies. The HSA binding to the polymyxins was relatively strong (Ka ≈ 1.0 × 107 M-1). Molecular docking indicated that polymyxins bind to the cleft of HSA between domains I and III via the electrostatic interactions. This evidence was further confirmed by the entropy-driven interaction for the polymyxins bound HSA. Far UV-CD experiments showed that the secondary structure of HSA doesn't alter and its stable structure is preserved. Collectively, these investigations revealed that the polymyxins bind preferentially to the partially unfolded intermediate forms of the protein structure; however, HSA molecule does not undergo any significant conformational changes upon binding. This is promising as it may limit the unfavorable side effects of the medicine. On the whole, the results provide quantitative and qualitative insight of the binding interaction between HSA and polymyxins, which is important in understanding their effect as therapeutic agents.

A direct calorimetric determination of denaturation enthalpy for lysozyme in sodium dodecyl sulfate.

Thermodynamics of the interaction between sodium dodecyl sulfate (SDS) with lysozyme were investigated at pH 7.0 and 27 degrees C in phosphate buffer by isothermal titration calorimetry. A new method to follow protein denaturation, and the effect of surfactants on the stability of proteins was introduced. The new solvation model was used to reproduce the enthalpies of lysozyme-SDS interaction over the whole range of SDS concentrations. The solvation parameters recovered from the new equation, attributed to the structural change of lysozyme and its biological activity. At low concentrations of SDS, the binding is mainly electrostatic, with some simultaneous interaction of the hydrophobic tail with nearby hydrophobic patches on the lysozyme. These initial interactions presumably cause some protein unfolding and expose additional hydrophobic sites. The enthalpy of denaturation is 160.81+/-0.02 kJ mol(-1) for SDS.

Thermodynamic study of the binding of calcium and magnesium ions with myelin basic protein using the extended solvation theory.

The interaction of myelin basic protein (MBP) from the bovine central nervous system with Ca2+ and Mg2+ ions, named as M2+, was studied by isothermal titration calorimetry at 27 degrees C in aqueous solution. The extended solvation model was used to reproduce the enthalpies of MBP+M2+ interactions. The solvation parameters recovered from the extended solvation model were attributed to the structural change of MBP due to the metal ion interaction. It was found that there is a set of two identical and noninteracting binding sites for Ca2+ and Mg2+ ions.

Determination of partial unfolding enthalpy for lysozyme upon interaction with dodecyltrimethylammonium bromide using an extended solvation model.

The interactions of dodecyltrimethylammonium bromides (DTABs) with hen egg lysozyme have been investigated at pH = 7.0 and 27 degrees C in phosphate buffer by isothermal titration calorimetry. DTAB interacts endothermically and activate lysozyme. The endothermicity of the lysozyme-DTAB interaction is in marked contrast to the exothermic interactions between sodium dodecyl sulphate (SDS) and lysozyme which have been attributed to specific binding between the anionic sulphate head groups and cationic amino acid residues. The enthalpies of interaction between the cationic surfactant (DTAB) and lysozyme are dominated by the endothermic unfolding of the native structure followed by an exothermic solvation of the lysozyme-DTAB complex by the addition of extra DTAB. A new direct calorimetric method to follow protein denaturation, and the effect of surfactants on the stability of proteins was introduced. The extended solvation model was used to reproduce the enthalpies of lysozyme-DTAB interaction over the whole range of DTAB concentrations. The solvation parameters recovered from the new equation, attributed to the structural change of lysozyme and its biological activity. At low concentrations of DTAB, the binding is mainly electrostatic, with some simultaneous interaction of the hydrophobic tail with nearby hydrophobic patches on the lysozyme. These initial interactions presumably cause some protein unfolding and expose additional hydrophobic sites. The DTAB-induced denaturation enthalpy of lysozyme is 86.46 +/- 0.02 kJ mol(-1).