Polyol and Sugar Osmolytes Can Shorten Protein Hydrogen Bonds to Modulate Function

Overview

Journal Commun Biol

Specialty Biology

Date 2020 Sep 24

PMID 32968183

Citations 11

Authors

Jingwen Li

Jingfei Chen

Liaoyuan An

Xiaoxiang Yuan

Lishan Yao

Affiliations

Soon will be listed here.

Abstract

Polyol and sugar osmolytes are commonly used in therapeutic protein formulations. How they may affect protein structure and function is an important question. In this work, through NMR measurements, we show that glycerol and sorbitol (polyols), as well as glucose (sugar), can shorten protein backbone hydrogen bonds. The hydrogen bond shortening is also captured by molecular dynamics simulations, which suggest a hydrogen bond competition mechanism. Specifically, osmolytes weaken hydrogen bonds between the protein and solvent to strengthen those within the protein. Although the hydrogen bond change is small, with the average experimental cross hydrogen bond J coupling of two proteins GB3 and TTHA increased by ~ 0.01 Hz by the three osmolytes (160 g/L), its effect on protein function should not be overlooked. This is exemplified by the PDZ3-peptide binding where several intermolecular hydrogen bonds are formed and osmolytes shift the equilibrium towards the bound state.

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References

Patriksson A, van der Spoel D . A temperature predictor for parallel tempering simulations. Phys Chem Chem Phys. 2008; 10(15):2073-7. DOI: 10.1039/b716554d. View

Persson F, Halle B . How amide hydrogens exchange in native proteins. Proc Natl Acad Sci U S A. 2015; 112(33):10383-8. PMC: 4547260. DOI: 10.1073/pnas.1506079112. View

Gao J, Bosco D, Powers E, Kelly J . Localized thermodynamic coupling between hydrogen bonding and microenvironment polarity substantially stabilizes proteins. Nat Struct Mol Biol. 2009; 16(7):684-90. PMC: 2754385. DOI: 10.1038/nsmb.1610. View

Roy S, Henderson I, Nayar R, Randolph T, Carpenter J . Effect of pH on stability of recombinant botulinum serotype A vaccine in aqueous solution and during storage of freeze-dried formulations. J Pharm Sci. 2008; 97(12):5132-46. DOI: 10.1002/jps.21409. View

Auton M, Bolen D . Predicting the energetics of osmolyte-induced protein folding/unfolding. Proc Natl Acad Sci U S A. 2005; 102(42):15065-8. PMC: 1257718. DOI: 10.1073/pnas.0507053102. View

Ferreon A, Moosa M, Gambin Y, Deniz A . Counteracting chemical chaperone effects on the single-molecule α-synuclein structural landscape. Proc Natl Acad Sci U S A. 2012; 109(44):17826-31. PMC: 3497778. DOI: 10.1073/pnas.1201802109. View

Delaglio F, Grzesiek S, Vuister G, Zhu G, Pfeifer J, Bax A . NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J Biomol NMR. 1995; 6(3):277-93. DOI: 10.1007/BF00197809. View

Sharp K . Analysis of the size dependence of macromolecular crowding shows that smaller is better. Proc Natl Acad Sci U S A. 2015; 112(26):7990-5. PMC: 4491746. DOI: 10.1073/pnas.1505396112. View

Zhang N, An L, Li J, Liu Z, Yao L . Quinary Interactions Weaken the Electric Field Generated by Protein Side-Chain Charges in the Cell-like Environment. J Am Chem Soc. 2017; 139(2):647-654. DOI: 10.1021/jacs.6b11058. View

10.

Wang L, Fried S, Boxer S, Markland T . Quantum delocalization of protons in the hydrogen-bond network of an enzyme active site. Proc Natl Acad Sci U S A. 2014; 111(52):18454-9. PMC: 4284547. DOI: 10.1073/pnas.1417923111. View

11.

Tiwari A, Bhat R . Stabilization of yeast hexokinase A by polyol osmolytes: correlation with the physicochemical properties of aqueous solutions. Biophys Chem. 2006; 124(2):90-9. DOI: 10.1016/j.bpc.2006.06.003. View

12.

Liao Y, Manson A, DeLyser M, Noid W, Cremer P . Trimethylamine -oxide stabilizes proteins via a distinct mechanism compared with betaine and glycine. Proc Natl Acad Sci U S A. 2017; 114(10):2479-2484. PMC: 5347566. DOI: 10.1073/pnas.1614609114. View

13.

Newberry R, Raines R . A prevalent intraresidue hydrogen bond stabilizes proteins. Nat Chem Biol. 2016; 12(12):1084-1088. PMC: 5110370. DOI: 10.1038/nchembio.2206. View

14.

Ma J, Pazos I, Gai F . Microscopic insights into the protein-stabilizing effect of trimethylamine N-oxide (TMAO). Proc Natl Acad Sci U S A. 2014; 111(23):8476-81. PMC: 4060645. DOI: 10.1073/pnas.1403224111. View

15.

Auton M, Rosgen J, Sinev M, Holthauzen L, Bolen D . Osmolyte effects on protein stability and solubility: a balancing act between backbone and side-chains. Biophys Chem. 2011; 159(1):90-9. PMC: 3166983. DOI: 10.1016/j.bpc.2011.05.012. View

16.

Vanommeslaeghe K, Hatcher E, Acharya C, Kundu S, Zhong S, Shim J . CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J Comput Chem. 2009; 31(4):671-90. PMC: 2888302. DOI: 10.1002/jcc.21367. View

17.

Sakakibara D, Sasaki A, Ikeya T, Hamatsu J, Hanashima T, Mishima M . Protein structure determination in living cells by in-cell NMR spectroscopy. Nature. 2009; 458(7234):102-5. DOI: 10.1038/nature07814. View

18.

Das A, Basak P, Pattanayak R, Kar T, Majumder R, Pal D . Trehalose induced structural modulation of Bovine Serum Albumin at ambient temperature. Int J Biol Macromol. 2017; 105(Pt 1):645-655. DOI: 10.1016/j.ijbiomac.2017.07.074. View

19.

Ohtake S, Wang Y . Trehalose: current use and future applications. J Pharm Sci. 2011; 100(6):2020-53. DOI: 10.1002/jps.22458. View

20.

Rydeen A, Brustad E, Pielak G . Osmolytes and Protein-Protein Interactions. J Am Chem Soc. 2018; 140(24):7441-7444. DOI: 10.1021/jacs.8b03903. View