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Structure-Energy Relationships of Halogen Bonds in Proteins.

Scholfield MR, Ford MC, Carlsson AC, Butta H, Mehl RA, Ho PS
Biochemistry 56 2794-2802 (2017)
Related entries: 5khz, 5ki1, 5ki2, 5ki8, 5kig, 5kii, 5kim, 5kio

Cited: 23 times
EuropePMC logo PMID: 28345933

Abstract

The structures and stabilities of proteins are defined by a series of weak noncovalent electrostatic, van der Waals, and hydrogen bond (HB) interactions. In this study, we have designed and engineered halogen bonds (XBs) site-specifically to study their structure-energy relationship in a model protein, T4 lysozyme. The evidence for XBs is the displacement of the aromatic side chain toward an oxygen acceptor, at distances that are equal to or less than the sums of their respective van der Waals radii, when the hydroxyl substituent of the wild-type tyrosine is replaced by a halogen. In addition, thermal melting studies show that the iodine XB rescues the stabilization energy from an otherwise destabilizing substitution (at an equivalent noninteracting site), indicating that the interaction is also present in solution. Quantum chemical calculations show that the XB complements an HB at this site and that solvent structure must also be considered in trying to design molecular interactions such as XBs into biological systems. A bromine substitution also shows displacement of the side chain, but the distances and geometries do not indicate formation of an XB. Thus, we have dissected the contributions from various noncovalent interactions of halogens introduced into proteins, to drive the application of XBs, particularly in biomolecular design.

Reviews citing this publication (5)

  1. Hydrogen Bond Enhanced Halogen Bonds: A Synergistic Interaction in Chemistry and Biochemistry. Riel AMS, Rowe RK, Ho EN, Carlsson AC, Rappé AK, Berryman OB, Ho PS. Acc Chem Res 52 2870-2880 (2019)
  2. A Novel Action of Endocrine-Disrupting Chemicals on Wildlife; DDT and Its Derivatives Have Remained in the Environment. Matsushima A. Int J Mol Sci 19 E1377 (2018)
  3. A Halogen Bonding Perspective on Iodothyronine Deiodinase Activity. Marsan ES, Bayse CA. Molecules 25 E1328 (2020)
  4. The Realm of Unconventional Noncovalent Interactions in Proteins: Their Significance in Structure and Function. Adhav VA, Saikrishnan K. ACS Omega 8 22268-22284 (2023)
  5. Non-canonical amino acids as a tool for the thermal stabilization of enzymes. Lugtenburg T, Gran-Scheuch A, Drienovská I. Protein Eng Des Sel 36 gzad003 (2023)

Articles citing this publication (18)

  1. Do Halogen-Hydrogen Bond Donor Interactions Dominate the Favorable Contribution of Halogens to Ligand-Protein Binding? Lin FY, MacKerell AD. J Phys Chem B 121 6813-6821 (2017)
  2. Halogen Bonding: A Powerful Tool for Modulation of Peptide Conformation. Danelius E, Andersson H, Jarvoll P, Lood K, Gräfenstein J, Erdélyi M. Biochemistry 56 3265-3272 (2017)
  3. Increasing Enzyme Stability and Activity through Hydrogen Bond-Enhanced Halogen Bonds. Carlsson AC, Scholfield MR, Rowe RK, Ford MC, Alexander AT, Mehl RA, Ho PS. Biochemistry 57 4135-4147 (2018)
  4. Polarizable Empirical Force Field for Halogen-Containing Compounds Based on the Classical Drude Oscillator. Lin FY, MacKerell AD. J Chem Theory Comput 14 1083-1098 (2018)
  5. The small molecule GAT1508 activates brain-specific GIRK1/2 channel heteromers and facilitates conditioned fear extinction in rodents. Xu Y, Cantwell L, Molosh AI, Plant LD, Gazgalis D, Fitz SD, Dustrude ET, Yang Y, Kawano T, Garai S, Noujaim SF, Shekhar A, Logothetis DE, Thakur GA. J Biol Chem 295 3614-3634 (2020)
  6. Structural basis for ligand recognition of the neuropeptide Y Y2 receptor. Tang T, Hartig C, Chen Q, Zhao W, Kaiser A, Zhang X, Zhang H, Qu H, Yi C, Ma L, Han S, Zhao Q, Beck-Sickinger AG, Wu B. Nat Commun 12 737 (2021)
  7. Efficient Site-Specific Prokaryotic and Eukaryotic Incorporation of Halotyrosine Amino Acids into Proteins. Jang HS, Gu X, Cooley RB, Porter JJ, Henson RL, Willi T, DiDonato JA, Hazen SL, Mehl RA. ACS Chem Biol 15 562-574 (2020)
  8. A rare example of a phosphine as a halogen bond acceptor. Xu Y, Huang J, Gabidullin B, Bryce DL. Chem Commun (Camb) 54 11041-11043 (2018)
  9. Site specificity of halogen bonding involving aromatic acceptors. Ang SJ, Mak AM, Sullivan MB, Wong MW. Phys Chem Chem Phys 20 8685-8694 (2018)
  10. Modeling halogen bonding with planewave density functional theory: Accuracy and challenges. Ang SJ, Ser CT, Wong MW. J Comput Chem 40 1829-1835 (2019)
  11. Pushing the Limits of Characterising a Weak Halogen Bond in Solution. Peintner S, Erdélyi M. Chemistry 28 e202103559 (2022)
  12. Halogen-bonding-induced diverse aggregation of 4,5-diiodo-1,2,3-triazolium salts with different anions. Xu X, Huang S, Zhang Z, Cao L, Yan X. Beilstein J Org Chem 16 78-87 (2020)
  13. Halogenation of the N-Terminus Tyrosine 10 Promotes Supramolecular Stabilization of the Amyloid-β Sequence 7-12. Maiolo D, Pizzi A, Gori A, Gazzera L, Demitri N, Genoni A, Baggi F, Moda F, Terraneo G, Baldelli Bombelli F, Metrangolo P, Resnati G. ChemistryOpen 9 253-260 (2020)
  14. High-Accuracy Prediction of Stabilizing Surface Mutations to the Three-Helix Bundle, UBA(1), with EmCAST. Rothfuss MT, Becht DC, Zeng B, McClelland LJ, Yates-Hansen C, Bowler BE. J Am Chem Soc 145 22979-22992 (2023)
  15. Predicting Blood-Brain Barrier Permeation of Erlotinib and JCN037 by Molecular Simulation. Liang Y, Zhi S, Qiao Z, Meng F. J Membr Biol 256 147-157 (2023)
  16. Probing halogen-halogen interactions in solution. Ayzac V, Raynal M, Isare B, Idé J, Brocorens P, Lazzaroni R, Etienne T, Monari A, Assfeld X, Bouteiller L. Phys Chem Chem Phys 19 32443-32450 (2017)
  17. Synthesis of Amino Acids Bearing Halodifluoromethyl Moieties and Their Application to p53-Derived Peptides Binding to Mdm2/Mdm4. Vaas S, Zimmermann MO, Klett T, Boeckler FM. Drug Des Devel Ther 17 1247-1274 (2023)
  18. The interplay between hydrogen and halogen bonding: substituent effects and their role in the hydrogen bond enhanced halogen bond. Sun J, Decato DA, Bryantsev VS, John EA, Berryman OB. Chem Sci 14 8924-8935 (2023)


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