title: Predictability of weak binding from X-ray crystallography: inhaled anesthetics and myoglobin.
abstract: 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.
authors: Department of Anesthesia, University of Pennsylvania, Philadelphia 19104, USA. tannerj@mail.med.upenn.edu
authors: J W
authors: JW
authors: Tanner
authors: J S
authors: JS
authors: Johansson
authors: P A
authors: PA
authors: Liebman
authors: R G
authors: RG
authors: Eckenhoff
mesh_terms: D018685:Anesthetics, Inhalation / Q000737:chemistry*; D000818:Animals; D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D018360:Crystallography, X-Ray / Q000379:methods; D006736:Horses; D006859:Hydrogen / Q000737:chemistry; D008752:Methylene Chloride / Q000737:chemistry*; D009211:Myoglobin / Q000737:chemistry*; D011485:Protein Binding; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry; D013816:Thermodynamics; D014316:Tritium / Q000737:chemistry; D014907:Whales; D014978:Xenon / Q000737:chemistry
chemical_list: D018685:Anesthetics, Inhalation; D009211:Myoglobin; D011994:Recombinant Proteins; D014316:Tritium; D014978:Xenon; D008752:Methylene Chloride; D006859:Hydrogen