n-Dodecyl β-D-maltoside specifically competes with general anesthetics for anesthetic binding sites.
We recently demonstrated that the anionic detergent sodium dodecyl sulfate (SDS) specifically interacts with the anesthetic binding site in horse spleen apoferritin, a soluble protein which models anesthetic binding sites in receptors. This raises the possibility of other detergents similarly interacting with and occluding such sites from anesthetics, thereby preventing the proper identification of novel anesthetic binding sites. n-Dodecyl β-D-maltoside (DDM) is a non-ionic detergent commonly used during protein-anesthetic studies because of its mild and non-denaturing properties. In this study, we demonstrate that SDS and DDM occupy anesthetic binding sites in the model proteins human serum albumin (HSA) and horse spleen apoferritin and thereby inhibit the binding of the general anesthetics propofol and isoflurane. DDM specifically interacts with HSA (Kd = 40 μM) with a lower affinity than SDS (Kd = 2 μM). DDM exerts all these effects while not perturbing the native structures of either model protein. Computational calculations corroborated the experimental results by demonstrating that the binding sites for DDM and both anesthetics on the model proteins overlapped. Collectively, our results indicate that DDM and SDS specifically interact with anesthetic binding sites and may thus prevent the identification of novel anesthetic sites. Special precaution should be taken when undertaking and interpreting results from protein-anesthetic investigations utilizing detergents like SDS and DDM.
a Department of Anesthesiology and Critical Care , Perelman School of Medicine at the University of Pennsylvania , 336 John Morgan Building, 3620 Hamilton Walk, Philadelphia , PA , USA .
Longhe
L
Xu
Felipe
F
Matsunaga
Jin
J
Xi
Min
M
Li
Jingyuan
J
Ma
Renyu
R
Liu
D018681:Anesthetics, General / Q000737:chemistry*; D001052:Apoferritins / Q000737:chemistry; D001665:Binding Sites; D002151:Calorimetry; D002942:Circular Dichroism; D005960:Glucosides / Q000737:chemistry*; D006801:Humans; D007530:Isoflurane / Q000737:chemistry; D062105:Molecular Docking Simulation; D015742:Propofol / Q000737:chemistry; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D013816:Thermodynamics
D018681:Anesthetics, General; D005960:Glucosides; D012709:Serum Albumin; D012967:Sodium Dodecyl Sulfate; C040358:dodecyl maltoside; D001052:Apoferritins; D007530:Isoflurane; D015742:Propofol
anesthetics; docking; protein; protein drug interactions; structure; thermodynamics