3f39 › Citations

A unitary anesthetic binding site at high resolution.

Vedula LS, Brannigan G, Economou NJ, Xi J, Hall MA, Liu R, Rossi MJ, Dailey WP, Grasty KC, Klein ML, Eckenhoff RG, Loll PJ
J Biol Chem 284 24176-84 (2009)
Related entries: 3f32, 3f33, 3f34, 3f35, 3f36, 3f37, 3f38

Cited: 45 times
EuropePMC logo PMID: 19605349

Abstract

Propofol is the most widely used injectable general anesthetic. Its targets include ligand-gated ion channels such as the GABA(A) receptor, but such receptor-channel complexes remain challenging to study at atomic resolution. Until structural biology methods advance to the point of being able to deal with systems such as the GABA(A) receptor, it will be necessary to use more tractable surrogates to probe the molecular details of anesthetic recognition. We have previously shown that recognition of inhalational general anesthetics by the model protein apoferritin closely mirrors recognition by more complex and clinically relevant protein targets; here we show that apoferritin also binds propofol and related GABAergic anesthetics, and that the same binding site mediates recognition of both inhalational and injectable anesthetics. Apoferritin binding affinities for a series of propofol analogs were found to be strongly correlated with the ability to potentiate GABA responses at GABA(A) receptors, validating this model system for injectable anesthetics. High resolution x-ray crystal structures reveal that, despite the presence of hydrogen bond donors and acceptors, anesthetic recognition is mediated largely by van der Waals forces and the hydrophobic effect. Molecular dynamics simulations indicate that the ligands undergo considerable fluctuations about their equilibrium positions. Finally, apoferritin displays both structural and dynamic responses to anesthetic binding, which may mimic changes elicited by anesthetics in physiologic targets like ion channels.

Articles - 3f39 mentioned but not cited (5)

  1. A unitary anesthetic binding site at high resolution. Vedula LS, Brannigan G, Economou NJ, Xi J, Hall MA, Liu R, Rossi MJ, Dailey WP, Grasty KC, Klein ML, Eckenhoff RG, Loll PJ. J Biol Chem 284 24176-24184 (2009)
  2. Cryo-EM single-particle structure refinement and map calculation using Servalcat. Yamashita K, Palmer CM, Burnley T, Murshudov GN. Acta Crystallogr D Struct Biol 77 1282-1291 (2021)
  3. Recognition of anesthetic barbiturates by a protein binding site: a high resolution structural analysis. Oakley S, Vedula LS, Bu W, Meng QC, Xi J, Liu R, Eckenhoff RG, Loll PJ. PLoS One 7 e32070 (2012)
  4. On the Use of Interaction Entropy and Related Methods to Estimate Binding Entropies. Ekberg V, Ryde U. J Chem Theory Comput 17 5379-5391 (2021)
  5. Comparison of Grand Canonical and Conventional Molecular Dynamics Simulation Methods for Protein-Bound Water Networks. Ekberg V, Samways ML, Misini Ignjatović M, Essex JW, Ryde U. ACS Phys Chem Au 2 247-259 (2022)


Reviews citing this publication (4)

  1. Iatrogenic risk factors for Alzheimer's disease: surgery and anesthesia. Vanderweyde T, Bednar MM, Forman SA, Wolozin B. J Alzheimers Dis 22 Suppl 3 91-104 (2010)
  2. Shedding Light on Anesthetic Mechanisms: Application of Photoaffinity Ligands. Woll KA, Dailey WP, Brannigan G, Eckenhoff RG. Anesth Analg 123 1253-1262 (2016)
  3. Molecular approaches to improving general anesthetics. Forman SA. Anesthesiol Clin 28 761-771 (2010)
  4. The Molecular Mechanisms of Anesthetic Action: Updates and Cutting Edge Developments from the Field of Molecular Modeling. Bertaccini EJ. Pharmaceuticals (Basel) 3 2178-2196 (2010)

Articles citing this publication (36)

  1. X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel. Nury H, Van Renterghem C, Weng Y, Tran A, Baaden M, Dufresne V, Changeux JP, Sonner JM, Delarue M, Corringer PJ. Nature 469 428-431 (2011)
  2. Multiple binding sites for the general anesthetic isoflurane identified in the nicotinic acetylcholine receptor transmembrane domain. Brannigan G, LeBard DN, Hénin J, Eckenhoff RG, Klein ML. Proc Natl Acad Sci U S A 107 14122-14127 (2010)
  3. m-Azipropofol (AziPm) a photoactive analogue of the intravenous general anesthetic propofol. Hall MA, Xi J, Lor C, Dai S, Pearce R, Dailey WP, Eckenhoff RG. J Med Chem 53 5667-5675 (2010)
  4. General anesthetics predicted to block the GLIC pore with micromolar affinity. LeBard DN, Hénin J, Eckenhoff RG, Klein ML, Brannigan G. PLoS Comput Biol 8 e1002532 (2012)
  5. Structure of the M2 transmembrane segment of GLIC, a prokaryotic Cys loop receptor homologue from Gloeobacter violaceus, probed by substituted cysteine accessibility. Parikh RB, Bali M, Akabas MH. J Biol Chem 286 14098-14109 (2011)
  6. Anesthetic binding in a pentameric ligand-gated ion channel: GLIC. Chen Q, Cheng MH, Xu Y, Tang P. Biophys J 99 1801-1809 (2010)
  7. A Single phenylalanine residue in the main intracellular loop of α1 γ-aminobutyric acid type A and glycine receptors influences their sensitivity to propofol. Moraga-Cid G, Yevenes GE, Schmalzing G, Peoples RW, Aguayo LG. Anesthesiology 115 464-473 (2011)
  8. Novel activation of voltage-gated K(+) channels by sevoflurane. Barber AF, Liang Q, Covarrubias M. J Biol Chem 287 40425-40432 (2012)
  9. Molecular mapping of general anesthetic sites in a voltage-gated ion channel. Barber AF, Liang Q, Amaral C, Treptow W, Covarrubias M. Biophys J 101 1613-1622 (2011)
  10. Assessment of homology templates and an anesthetic binding site within the γ-aminobutyric acid receptor. Bertaccini EJ, Yoluk O, Lindahl ER, Trudell JR. Anesthesiology 119 1087-1095 (2013)
  11. Direct modulation of microtubule stability contributes to anthracene general anesthesia. Emerson DJ, Weiser BP, Psonis J, Liao Z, Taratula O, Fiamengo A, Wang X, Sugasawa K, Smith AB, Eckenhoff RG, Dmochowski IJ. J Am Chem Soc 135 5389-5398 (2013)
  12. Binding site and affinity prediction of general anesthetics to protein targets using docking. Liu R, Perez-Aguilar JM, Liang D, Saven JG. Anesth Analg 114 947-955 (2012)
  13. Pressure-response analysis of anesthetic gases xenon and nitrous oxide on urate oxidase: a crystallographic study. Marassio G, Prangé T, David HN, Santos JS, Gabison L, Delcroix N, Abraini JH, Colloc'h N. FASEB J 25 2266-2275 (2011)
  14. Role for the propofol hydroxyl in anesthetic protein target molecular recognition. Woll KA, Weiser BP, Liang Q, Meng T, McKinstry-Wu A, Pinch B, Dailey WP, Gao WD, Covarrubias M, Eckenhoff RG. ACS Chem Neurosci 6 927-935 (2015)
  15. Anesthetic drug development: Novel drugs and new approaches. Chitilian HV, Eckenhoff RG, Raines DE. Surg Neurol Int 4 S2-S10 (2013)
  16. Unresponsive correlated motion in alpha7 nAChR to halothane binding explains its functional insensitivity to volatile anesthetics. Mowrey D, Haddadian EJ, Liu LT, Willenbring D, Xu Y, Tang P. J Phys Chem B 114 7649-7655 (2010)
  17. Propofol shares the binding site with isoflurane and sevoflurane on leukocyte function-associated antigen-1. Yuki K, Bu W, Xi J, Shimaoka M, Eckenhoff R. Anesth Analg 117 803-811 (2013)
  18. A Novel Bifunctional Alkylphenol Anesthetic Allows Characterization of γ-Aminobutyric Acid, Type A (GABAA), Receptor Subunit Binding Selectivity in Synaptosomes. Woll KA, Murlidaran S, Pinch BJ, Hénin J, Wang X, Salari R, Covarrubias M, Dailey WP, Brannigan G, Garcia BA, Eckenhoff RG. J Biol Chem 291 20473-20486 (2016)
  19. Ferritin couples iron and fatty acid metabolism. Bu W, Liu R, Cheung-Lau JC, Dmochowski IJ, Loll PJ, Eckenhoff RG. FASEB J 26 2394-2400 (2012)
  20. A semiempirical approach to ligand-binding affinities: dependence on the Hamiltonian and corrections. Mikulskis P, Genheden S, Wichmann K, Ryde U. J Comput Chem 33 1179-1189 (2012)
  21. Inhalational anaesthetics and n-alcohols share a site of action in the neuronal Shaw2 Kv channel. Bhattacharji A, Klett N, Go RC, Covarrubias M. Br J Pharmacol 159 1475-1485 (2010)
  22. Effect of explicit water molecules on ligand-binding affinities calculated with the MM/GBSA approach. Mikulskis P, Genheden S, Ryde U. J Mol Model 20 2273 (2014)
  23. Crystallographic studies with xenon and nitrous oxide provide evidence for protein-dependent processes in the mechanisms of general anesthesia. Abraini JH, Marassio G, David HN, Vallone B, Prangé T, Colloc'h N. Anesthesiology 121 1018-1027 (2014)
  24. Discovery of a novel general anesthetic chemotype using high-throughput screening. McKinstry-Wu AR, Bu W, Rai G, Lea WA, Weiser BP, Liang DF, Simeonov A, Jadhav A, Maloney DJ, Eckenhoff RG. Anesthesiology 122 325-333 (2015)
  25. Sites and Functional Consequence of Alkylphenol Anesthetic Binding to Kv1.2 Channels. Bu W, Liang Q, Zhi L, Maciunas L, Loll PJ, Eckenhoff RG, Covarrubias M. Mol Neurobiol 55 1692-1702 (2018)
  26. Ketamine Metabolite (2R,6R)-Hydroxynorketamine Interacts with μ and κ Opioid Receptors. Joseph TT, Bu W, Lin W, Zoubak L, Yeliseev A, Liu R, Eckenhoff RG, Brannigan G. ACS Chem Neurosci 12 1487-1497 (2021)
  27. The discovery of new anesthetics by targeting GABA(A) receptors. Krasowski MD, Hopfinger AJ. Expert Opin Drug Discov 6 1187-1201 (2011)
  28. Detection of glycosylation and iron-binding protein modifications using Raman spectroscopy. Ashton L, Brewster VL, Correa E, Goodacre R. Analyst 142 808-814 (2017)
  29. Screening Europe 2010: an update about the latest technologies and applications in high-throughput screening. Merten CA. Expert Rev Mol Diagn 10 559-563 (2010)
  30. Can MM/GBSA calculations be sped up by system truncation? Misini Ignjatović M, Mikulskis P, Söderhjelm P, Ryde U. J Comput Chem 39 361-372 (2018)
  31. Evaluation of crystal quality of thin protein crystals based on the dynamical theory of X-ray diffraction. Abe M, Suzuki R, Kojima K, Tachibana M. IUCrJ 7 761-766 (2020)
  32. Molecular Mechanics Parameterization of Anesthetic Molecules. Joseph TT, Hénin J. Methods Enzymol 602 61-76 (2018)
  33. Solvent flows, conformation changes and lattice reordering in a cold protein crystal. Moreau DW, Atakisi H, Thorne RE. Acta Crystallogr D Struct Biol 75 980-994 (2019)
  34. Synthesis and Characterization of a Diazirine-Based Photolabel of the Nonanesthetic Fropofol. White ER, Leace DM, Bedell VM, Bhanu NV, Garcia BA, Dailey WP, Eckenhoff RG. ACS Chem Neurosci 12 176-183 (2021)
  35. ASAXS measurements on ferritin and apoferritin at the bioSAXS beamline P12 (PETRA III, DESY). Wieland DCF, Schroer MA, Gruzinov AY, Blanchet CE, Jeffries CM, Svergun DI. J Appl Crystallogr 54 830-838 (2021)
  36. n-Dodecyl β-D-maltoside specifically competes with general anesthetics for anesthetic binding sites. Xu L, Matsunaga F, Xi J, Li M, Ma J, Liu R. J Biomol Struct Dyn 32 1833-1840 (2014)


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