Abstract
S-containing amino acids can lead to two types of local NH···S interactions which bridge backbone NH sites to the side chain to form either intra- or inter-residue H-bonds. The present work reports on the conformational preferences of S-methyl-l-cysteine, Cys(Me), using a variety of investigating tools, ranging from quantum chemistry simulations, gas-phase UV and IR laser spectroscopy, and solution state IR and NMR spectroscopies, on model compounds comprising one or two Cys(Me) residues. We demonstrate that in gas phase and in low polarity solution, the C- and N-capped model compound for one Cys(Me) residue adopts a preferred C5–C6γ conformation which combines an intra-residue N–H···O=C backbone interaction (C5) and an inter-residue N–H···S interaction implicating the side-chain sulfur atom (C6γ). In contrast, the dominant conformation of the C- and N-capped model compound featuring two consecutive Cys(Me) residues is a regular type I β-turn. This structure is incompatible with concomitant C6γ interactions, which are no longer in evidence. Instead, C5γ interactions occur, that are fully consistent with the turn geometry and additionally stabilize the structure. Comparison with the thietane amino acid Attc, which exhibits a rigid cyclic side chain, pinpoints the significance of side chain flexibility for the specific conformational behavior of Cys(Me).
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alabugin IV, Gilmore KM, Peterson PW (2011) Hyperconjugation WIREs. Comput Mol Sci 1(1):109–141. https://doi.org/10.1002/wcms.6
Alabugin IV, Gomes GD, Abdo MA (2019) Hyperconjugation. WIREs Comput Mol Sci. https://doi.org/10.1002/wcms.1389
Alauddin M, Biswal HS, Gloaguen E, Mons M (2015) Intra-residue interactions in proteins: interplay between serine or cysteine side chains and backbone conformations, revealed by laser spectroscopy of isolated model peptides. Phys Chem Chem Phys 17(3):2169–2178. https://doi.org/10.1039/c4cp04449e
Amin MA, Khaled KF, Mohsen Q, Arida HA (2010) A study of the inhibition of iron corrosion in HCl solutions by some amino acids. Corrosion Sci 52(5):1684–1695. https://doi.org/10.1016/j.corsci.2010.01.019
Birdi KS, Fasman GD (1972) Monolayer studies of synthetic poly(alpha-amino acids). J Polymer Sci Part Polymer Chem 10(8):2483. https://doi.org/10.1002/pol.1972.150100824
Biswal HS, Gloaguen E, Loquais Y, Tardivel B, Mons M (2012) Strength of NH⋯S hydrogen bonds in methionine residues revealed by gas-phase IR/UV spectroscopy. J Phys Chem Lett 3(6):755–759. https://doi.org/10.1021/jz300207k
Bloom SM, Deloze C, Fasman GD, Blout ER (1962) Effect of amino acid composition on conformations of synthetic polypeptides, polymers and copolymers of L-methionine S-methyl-L-cysteine and L-valine. J Am Chem Soc 84(3):458–460. https://doi.org/10.1021/ja00862a027
Bonora GM, Maglione A, Toniolo C (1975) Linear oligopeptides. 24. Preparation of a series of monodisperse homopeptides (to heptamer) of S-methyl-l-cysteine. Gazz Chim Ital 105(9–10):1055–1062
Brenner V, Gloaguen E, Mons M (2019) Rationalizing the diversity of amide-amide h-bonding in peptides using the natural bond orbital method. Phys Chem Chem Phys 21(44):24601–24619. https://doi.org/10.1039/c9cp03825f
Cavallini D, Gauli GE, Zappia V (1980) Natural sulfur compounds: novel biochemical and structural aspects. Plenum Press, New York
Eichkorn K, Weigend F, Treutler O, Ahlrichs R (1997) Auxiliary basis sets for main row atoms and transition metals and their use to approximate Coulomb potentials. Theoret Chem Acc 97(1–4):119–124. https://doi.org/10.1007/s002140050244
Fasman GD, Potter J (1967) Optical rotatory dispersion of 2β structures. Biochem Biophys Res Commun 27(2):209–210. https://doi.org/10.1016/s0006-291x(67)80063-9
Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Petersson GA, Nakatsuji H, Li X, Caricato M, Marenich AV, Bloino J, Janesko BG, R. Gomperts R, Mennucci B, Hratchian HP, Ortiz JV, Izmaylov AF, Sonnenberg JL, Williams-Young D, Ding F, Lipparini F, Egidi F, Goings J, Peng B, Petrone A, Henderson T, Ranasinghe D, Zakrzewski VG, Gao J, Rega N, Zheng G, Liang W, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai N, Vreven T, Throssell K, Montgomery Jr. JA, Peralta JE, Ogliaro F, Bearpark MJ, Heyd JJ, Brothers EN, Kudin KN, Staroverov VN, Keith TA, Kobayashi R, Normand J, Raghavachari K, Rendell AP, Burant JC, Iyengar SS, Tomasi J, Cossi M, Millam JM, Klene M, Adamo C, Cammi R, Ochterski JW, Martin RL, Morokuma K, Farkas O, Foresman JB, Fox DJ, (2016) Gaussian 16. Revision A, 03 edn. Gaussian Inc, Wallingford
Gloaguen E, Mons M (2015) Isolated neutral peptides. Top Curr Chem 364:225–270. https://doi.org/10.1007/128_2014_580
Gloaguen E, de Courcy B, Piquemal JP, Pilme J, Parisel O, Pollet R, Biswal HS, Piuzzi F, Tardivel B, Broquier M, Mons M (2010a) Gas-phase folding of a two-residue model peptide chain: on the importance of an interplay between experiment and theory. J Am Chem Soc 132(34):11860–11863. https://doi.org/10.1021/ja103996q
Gloaguen E, Valdes H, Pagliarulo F, Pollet R, Tardivel B, Hobza P, Piuzzi F, Mons M (2010b) Experimental and theoretical investigation of the aromatic–aromatic interaction in isolated capped dipeptides. J Phys Chem A 114(9):2973–2982. https://doi.org/10.1021/jp904216f
Gloaguen E, Brenner V, Alauddin M, Tardivel B, Mons M, Zehnacker-Rentien A, Declerck V, Aitken DJ (2014) Direct spectroscopic evidence of hyperconjugation unveils the conformational landscape of hydrazides. Angewandte Chem Int Edition 53(50):13756–13759. https://doi.org/10.1002/anie.201407801
Gloaguen E, Mons M, Schwing K, Gerhards M (2020) Neutral peptides in the gas phase: conformation and aggregation issues. Chem Rev 120(22):12490–12562. https://doi.org/10.1021/acs.chemrev.0c00168
Goldsztejn G, Mundlapati V-R, Donon J, Tardivel B, Gloaguen E, Brenner V, Mons M (2020a) An intraresidue H-bonding motif in selenocysteine and cysteine, revealed by gas phase laser spectroscopy and quantum chemistry calculations. Phys Chem Chem Phys 22(36):20409–20420. https://doi.org/10.1039/D0CP02825H
Goldsztejn G, Mundlapati V, Brenner V, Gloaguen E, Mons M, León I, Cabezas C, Alonso JL (2020b) Intrinsic folding of the cysteine side chain: microwave and optical spectroscopic studies combined with quantum chemistry methods. Phys Chem Chem Phys 22:20284–20294. https://doi.org/10.1039/D0CP03136D
Grabarse WG, Mahlert F, Shima S, Thauer RK, Ermler U (2000) Comparison of three methyl-coenzyme M reductases from phylogenetically distant organisms: unusual amino acid modification, conservation and adaptation. J Mol Biol 303(2):329–344. https://doi.org/10.1006/jmbi.2000.4136
Grimme S, Antony J, Ehrlich S, Krieg H (2010) A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu. J Chem Phys. https://doi.org/10.1063/1.3382344
Imani Z, Mundlapati VR, Goldsztejn G, Brenner V, Gloaguen E, Guillot R, Baltaze JP, Le Barbu-Debus K, Robin S, Zehnacker A, Mons M, Aitken DJ (2020) Conformation control through concurrent N–H⋯S and N–H⋯O–C hydrogen bonding and hyperconjugation effects. Chem Sci 11(34):9191–9197. https://doi.org/10.1039/d0sc03339a
Komoto T, Oya M, Kawai T (1974) Crystallization of polypeptides in course of polymerization. 6. Effect of heteroatom attached to β-carbon on crystal-growth. Makromolekulare Chemie-Macromol Chem Phys 175(1):301–310. https://doi.org/10.1002/macp.1974.021750130
Lei M, Feng HY, Bai EH, Zhou H, Wang J, Qin YR, Zhang HY, Wang XY, Liu ZG, Hai O, Liu J, Zhu YQ (2019) Discovery of a novel dipeptidyl boronic acid proteasome inhibitor for the treatment of multiple myeloma and triple- negative breast cancer. Org Biomol Chem 17(3):683–691. https://doi.org/10.1039/c8ob02668h
Liu PX, Weng R, Sheng XJ, Wang XL, Zhang WH, Qian YZ, Qiu J (2020) Profiling of organosulfur compounds and amino acids in garlic from different regions of China. Food Chem. https://doi.org/10.1016/j.foodchem.2019.125499
Macromodel (2019) Schrödinger Release 2019-3. Schrödinger, LLC, New York, NY
Maw GA (1982) Biochemistry of S-methyl-l-cysteine and its principal derivatives. Sulfur Rep 2(1):1–26. https://doi.org/10.1080/01961778208082422
Mazumder MAJ (2019) Synthesis, characterization and electrochemical analysis of cysteine modified polymers for corrosion inhibition of mild steel in aqueous 1 M HCl (vol 9, pg 4277, 2019). Rsc Adv 9(11):6077–6077. https://doi.org/10.1039/c9ra90012h
Palumbo M, Darin S, Bonora GM, Toniolo C (1976) Linear oligopeptides. 29. Infrared conformational-analysis of homo-oligopeptides in solid-state and in solution. Makromolekulare Chemie-Macromol Chem Phys 177(5):1477–1492. https://doi.org/10.1002/macp.1976.021770519
Peggion C, Moretto A, Formaggio F, Crisma M, Toniolo C (2013) Multiple, consecutive, fully-extended 2.0(5)-helix peptide conformation. Biopolymers 100(6):621–636. https://doi.org/10.1002/bip.22267
Rao CP, Nagaraj R, Rao CNR, Balaram P (1980) Infrared studies on the conformation of synthetic alamethicin fragments and model peptides containing alpha-aminoisobutyric-acid. Biochemistry 19(3):425–431. https://doi.org/10.1021/bi00544a004
Rappoport D, Furche F (2010) Property-optimized Gaussian basis sets for molecular response calculations. J Chem Phys. https://doi.org/10.1063/1.3484283
Reed AE, Curtiss LA, Weinhold F (1988) Intermolecular interactions from a natural bond orbital. Donor-AcceptViewpoint Chem Rev 88(6):899–926. https://doi.org/10.1021/cr00088a005
Thompson JF (1967) Sulfur metabolism in plants. Ann Rev Plant Physiol 18:59. https://doi.org/10.1146/annurev.pp.18.060167.000423
Toniolo C (1980) Intramolecularly hydrogen-bonded peptide conformations. CRC Crit Rev Biochem 9(1):1–44. https://doi.org/10.3109/10409238009105471
Toniolo C, Bonora GM, Scatturin A (1975) Linear oligopeptides. 25. Effect of a sulfur atom in γ-position on secondary structures of homo-oligopeptides. Gazz Chim Ital 105(9–10):1063–1071
Turbomole (2017) V7.2. A development of University of Karlsruhe and Forschungszentrum Karlsruhe GmbH, 1989–2007, Turbomole GmbH, since 2007, available from http://www.turbomole.com.
Weinhold F (2012) Natural bond orbital analysis: A critical overview of relationships to alternative bonding perspectives. J Comput Chem 33(30):2363–2379. https://doi.org/10.1002/jcc.23060
Weinhold F, Reed AE, Carpenter JE, Glendening ED. NBO version 3.1. edn.,
Wróbel J (1977) Low molecular weight sulphur containing natural products. Pergamon Press, Oxford
Yan B, Jaeqx S, van der Zande WJ, Rijs AM (2014) A conformation-selective IR-UV study of the dipeptides Ac-Phe-Ser-NH2 and Ac-Phe-Cys-NH2: probing the SH⋯O and OH⋯O hydrogen bond interactions. Phys Chem Chem Phys 16(22):10770–10778. https://doi.org/10.1039/c4cp00810c
Zawistowski J, Kopec A, Jedrszczyk E, Francik R, Bystrowska B (2018) Garlic grown from air bulbils and its potential health benefits. In: Jayaprakasha GK, Patil BS, Gattuso G (eds) Advances in plant phenolics: from chemistry to human health, vol 1286. ACS Symposium Series, London, pp 315–328
Acknowledgements
The authors wish to thank Ms Roxanne Berthin and Ms Anna Kriukova for their theoretical contribution to the conformational explorations. Support from the French National Research Agency (ANR; Grant ANR-17-CE29-0008 "TUNIFOLD-S") and from the “Investissements d’Avenir” Funding program (LabEx PALM; grant ANR-10-LABX-0039-PALM; DIRCOS) are acknowledged. This work was granted access to the HPC facility of [TGCC/CINES/IDRIS] under the Grant 2019-A0050807540 awarded by GENCI (Grand Equipement National de Calcul Intensif) and to the CCRT High Performance Computing (HPC) facility at CEA under the Grant CCRT2019-p606bren.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving human participants and/or animals
This article does not contain any studies with human participants or animals performed by any of the authors.
Informed consent
This article does not contain individual participants requiring informed consent.
Additional information
Communicated by P. Meffre.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Mundlapati, V.R., Imani, Z., Goldsztejn, G. et al. A theoretical and experimental case study of the hydrogen bonding predilection of S-methylcysteine. Amino Acids 53, 621–633 (2021). https://doi.org/10.1007/s00726-021-02967-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00726-021-02967-z