Xenon and dichloromethane are inhalational anesthetic agents whose binding to myoglobin has been demonstrated by X-ray crystallography. We explore the thermodynamic significance of such binding using differential scanning calorimetry, circular dichroism spectroscopy, and hydrogen-tritium exchange measurements to study the effect of these agents on myoglobin folding stability. Though specific binding of these anesthetics might be expected to stabilize myoglobin against unfolding, dichloromethane actually destabilized myoglobin at all examined concentrations of this anesthetic (15, 40, and 200 mM). On the other hand, xenon (1 atm) stabilized myoglobin. Thus, dichloromethane and xenon have opposite effects on myoglobin stability despite localization in comparably folded X-ray crystallographic structures. These results suggest a need for solution measurements to complement crystallography if the consequences of weak binding to proteins are to be appreciated. Study holds ProTherm entries: 11758, 11759, 11760, 11761, 11762, 11763 Extra Details: inhalational anesthetic agents; folding stability; dichloromethane; xenon
Submitter: Connie Wang
Submission Date: April 24, 2018, 8:43 p.m.
|Number of data points||6|
|Proteins||Myoglobin ; Myoglobin|
|Assays/Quantities/Protocols||Experimental Assay: Tm buffers:dichloromethane: 200 mM ; Experimental Assay: Tm buffers:dichloromethane: 40 mM ; Experimental Assay: Tm buffers:dichloromethane: 0 mM ; Experimental Assay: Tm buffers:dichloromethane: 200 mM ; Experimental Assay: Tm buffers:dichloromethane: 40 mM ; Experimental Assay: Tm buffers:dichloromethane: 0 mM|
|Libraries||Mutations for sequence GLSDGEWQQVLNVWGKVEADIAGHGQEVLIRLFTGHPETLEKFDKFKHLKTEAEMKASEDLKKHGTVVLTALGGILKKKGHHEAELKPLAQSHATKHKIPIKYLEFISDAIIHVLHSKHPGDFGADAQGAMTKALELFRNDIAAKYKELGFQG|