4ygn Citations

Interactions between Hofmeister anions and the binding pocket of a protein.

J Am Chem Soc 137 3859-66 (2015)
Related entries: 4ygj, 4ygk, 4ygl

Cited: 39 times
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Abstract

This paper uses the binding pocket of human carbonic anhydrase II (HCAII, EC 4.2.1.1) as a tool to examine the properties of Hofmeister anions that determine (i) where, and how strongly, they associate with concavities on the surfaces of proteins and (ii) how, upon binding, they alter the structure of water within those concavities. Results from X-ray crystallography and isothermal titration calorimetry show that most anions associate with the binding pocket of HCAII by forming inner-sphere ion pairs with the Zn(2+) cofactor. In these ion pairs, the free energy of anion-Zn(2+) association is inversely proportional to the free energetic cost of anion dehydration; this relationship is consistent with the mechanism of ion pair formation suggested by the "law of matching water affinities". Iodide and bromide anions also associate with a hydrophobic declivity in the wall of the binding pocket. Molecular dynamics simulations suggest that anions, upon associating with Zn(2+), trigger rearrangements of water that extend up to 8 Å away from their surfaces. These findings expand the range of interactions previously thought to occur between ions and proteins by suggesting that (i) weakly hydrated anions can bind complementarily shaped hydrophobic declivities, and that (ii) ion-induced rearrangements of water within protein concavities can (in contrast with similar rearrangements in bulk water) extend well beyond the first hydration shells of the ions that trigger them. This study paints a picture of Hofmeister anions as a set of structurally varied ligands that differ in size, shape, and affinity for water and, thus, in their ability to bind to—and to alter the charge and hydration structure of—polar, nonpolar, and topographically complex concavities on the surfaces of proteins.

Articles - 4ygn mentioned but not cited (1)

  1. Interactions between Hofmeister anions and the binding pocket of a protein. Fox JM, Kang K, Sherman W, Héroux A, Sastry GM, Baghbanzadeh M, Lockett MR, Whitesides GM. J Am Chem Soc 137 3859-3866 (2015)


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  1. The Molecular Origin of Enthalpy/Entropy Compensation in Biomolecular Recognition. Fox JM, Zhao M, Fink MJ, Kang K, Whitesides GM. Annu Rev Biophys 47 223-250 (2018)
  2. Reconsidering anion inhibitors in the general context of drug design studies of modulators of activity of the classical enzyme carbonic anhydrase. Nocentini A, Angeli A, Carta F, Winum JY, Zalubovskis R, Carradori S, Capasso C, Donald WA, Supuran CT. J Enzyme Inhib Med Chem 36 561-580 (2021)
  3. The Chaotropic Effect as an Assembly Motif in Chemistry. Assaf KI, Nau WM. Angew Chem Int Ed Engl 57 13968-13981 (2018)
  4. Collaborative routes to clarifying the murky waters of aqueous supramolecular chemistry. Cremer PS, Flood AH, Gibb BC, Mobley DL. Nat Chem 10 8-16 (2017)
  5. Molecular Shape and the Hydrophobic Effect. Hillyer MB, Gibb BC. Annu Rev Phys Chem 67 307-329 (2016)
  6. Applications of isothermal titration calorimetry - the research and technical developments from 2011 to 2015. Falconer RJ. J Mol Recognit 29 504-515 (2016)
  7. Thermodynamic, kinetic, and structural parameterization of human carbonic anhydrase interactions toward enhanced inhibitor design. Linkuvienė V, Zubrienė A, Manakova E, Petrauskas V, Baranauskienė L, Zakšauskas A, Smirnov A, Gražulis S, Ladbury JE, Matulis D. Q Rev Biophys 51 e10 (2018)
  8. Ion specificities of artificial macromolecules. Liu L, Kou R, Liu G. Soft Matter 13 68-80 (2016)
  9. Redesign of water networks for efficient biocatalysis. Fink MJ, Syrén PO. Curr Opin Chem Biol 37 107-114 (2017)
  10. Relationship between Solvation Thermodynamics from IST and DFT Perspectives. Levy RM, Cui D, Zhang BW, Matubayasi N. J Phys Chem B 121 3825-3841 (2017)
  11. Biophysical, Biochemical, and Cell Based Approaches Used to Decipher the Role of Carbonic Anhydrases in Cancer and to Evaluate the Potency of Targeted Inhibitors. Mboge MY, Kota A, McKenna R, Frost SC. Int J Med Chem 2018 2906519 (2018)
  12. Ins and Outs of Rocker Switch Mechanism in Major Facilitator Superfamily of Transporters. Sauve S, Williamson J, Polasa A, Moradi M. Membranes (Basel) 13 462 (2023)
  13. When Molecules Meet in Water-Recent Contributions of Supramolecular Chemistry to the Understanding of Molecular Recognition Processes in Water. Kubik S. ChemistryOpen 11 e202200028 (2022)

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