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Cited by 9Advanced NMR Techniques and ApplicationsProtein Structure and DynamicsChemical Synthesis and Analysis

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Facilitating the structural characterisation of non-canonical amino acids in biomolecular NMR

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Kuschert, Sarah, Stroet, Martin, Chin, Yanni Ka-Yan, Conibear, Anne Claire, Jia, Xinying, Lee, Thomas, Bartling, Christian Reinhard Otto, Strømgaard, Kristian, Güntert, Peter, Rosengren, Karl Johan, Mark, Alan Edward, Mobli, Mehdi·2023·Magnetic Resonance
DOI 10.5194/mr-4-57-2023PMC PMC10583272

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Abstract

Peptides and proteins containing non-canonical amino acids (ncAAs) are a large and important class of biopolymers. They include non-ribosomally synthesised peptides, post-translationally modified proteins, expressed or synthesised proteins containing unnatural amino acids, and peptides and proteins that are chemically modified. Here, we describe a general procedure for generating atomic descriptions required to incorporate ncAAs within popular NMR structure determination software such as CYANA, CNS, Xplor-NIH and ARIA. This procedure is made publicly available via the existing Automated Topology Builder (ATB) server (https://atb.uq.edu.au, last access: 17 February 2023) with all submitted ncAAs stored in a dedicated database. The described procedure also includes a general method for linking of side chains of amino acids from CYANA templates. To ensure compatibility with other systems, atom names comply with IUPAC guidelines. In addition to describing the workflow, 3D models of complex natural products generated by CYANA are presented, including vancomycin. In order to demonstrate the manner in which the templates for ncAAs generated by the ATB can be used in practice, we use a combination of CYANA and CNS to solve the structure of a synthetic peptide designed to disrupt Alzheimer-related protein–protein interactions. Automating the generation of structural templates for ncAAs will extend the utility of NMR spectroscopy to studies of more complex biomolecules, with applications in the rapidly growing fields of synthetic biology and chemical biology. The procedures we outline can also be used to standardise the creation of structural templates for any amino acid and thus have the potential to impact structural biology more generally.

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Research works printed but not linked: 67

  1. Allain, F., Mareuil, F., Menager, H., Nilges, M., and Bardiaux, B.: ARIAweb: a server for automated NMR structure calculation, Nucleic Acids Res., 48, W41–W47, 10.1093/nar/gkaa362, 2020. · DOI
  2. Armstrong, D. A., Kaas, Q., and Rosengren, K. J.: Prediction of disulfide dihedral angles using chemical shifts, Chem. Sci., 9, 6548–6556, 10.1039/c8sc01423j, 2018. · DOI
  3. Barber, K. W. and Rinehart, J.: The ABCs of PTMs, Nat. Chem. Biol., 14, 188–192, 10.1038/nchembio.2572, 2018. · DOI
  4. Bartling, C. R. O., Alexopoulou, F., Kuschert, S., Chin, Y. K. Y., Jia, X., Sereikaite, V., Özcelik, D., Jensen, T. M., Jain, P., Nygaard, M. M., Harpsøe, K., Gloriam, D. E., Mobli, M., and Strømgaard, K.: Comprehensive Peptide Cyclization Examination Yields Optimized APP Scaffolds with Improved Affinity toward Mint2, J. Med. Chem., 10.1021/acs.jmedchem.2c02017, 2023. · DOI
  5. Bermejo, G. A. and Schwieters, C. D.: Protein Structure Elucidation from NMR Data with the Program Xplor-NIH, Methods Mol. Biol., 1688, 311–340, 10.1007/978-1-4939-7386-6_14, 2018. · DOI
  6. Bienfait, B. and Ertl, P.: JSME: a free molecule editor in JavaScript, J. Cheminformatics, 5, 24, 10.1186/1758-2946-5-24, 2013. · DOI
  7. Bondalapati, S., Jbara, M., and Brik, A.: Expanding the chemical toolbox for the synthesis of large and uniquely modified proteins, Nat. Chem., 8, 407–418, 10.1038/nchem.2476, 2016. · DOI
  8. Bottoms, C. A. and Xu, D.: Wanted: unique names for unique atom positions. PDB-wide analysis of diastereotopic atom names of small molecules containing diphosphate, BMC Bioinformatics, 9, S16, 10.1186/1471-2105-9-S9-S16, 2008. · DOI
  9. Brunger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse-Kunstleve, R. W., Jiang, J. S., Kuszewski, J., Nilges, M., Pannu, N. S., Read, R. J., Rice, L. M., Simonson, T., and Warren, G. L.: Crystallography & NMR system: A new software suite for macromolecular structure determination, Acta Crystallogr. D, 54, 905–921, 10.1107/s0907444998003254, 1998. · DOI
  10. Bullwinkle, T., Lazazzera, B., and Ibba, M.: Quality control and infiltration of translation by amino acids outside of the genetic code, Annu. Rev. Genet., 48, 149–166, 10.1146/annurev-genet-120213-092101, 2014. · DOI
  11. Caboche, S., Pupin, M., Leclere, V., Fontaine, A., Jacques, P., and Kucherov, G.: NORINE: a database of nonribosomal peptides, Nucleic Acids Res., 36, D326–331, 10.1093/nar/gkm792, 2008. · DOI
  12. Cahn, R. S. and Ingold, C. K.: 131. Specification of configuration about quadricovalent asymmetric atoms, J. Chem. Soc., 612–622, 10.1039/jr9510000612, 1951. · DOI
  13. Chuh, K. N., Batt, A. R., and Pratt, M. R.: Chemical Methods for Encoding and Decoding of Posttranslational Modifications, Cell Chem. Biol., 23, 86–107, 10.1016/j.chembiol.2015.11.006, 2016. · DOI
  14. Cieplak, T. and Wisniewski, J. L.: New Effective Algorithm for the Unambiguous Identification of the Stereochemical Characteristics of Compounds During Their Registration in Databases, Molecules, 6, 915–926, 10.3390/61100915, 2001. · DOI
  15. Coin, I.: Application of non-canonical crosslinking amino acids to study protein-protein interactions in live cells, Curr. Opin. Chem. Biol., 46, 156–163, 10.1016/j.cbpa.2018.07.019, 2018. · DOI
  16. Conibear, A. C.: Deciphering protein post-translational modifications using chemical biology tools, Nature Reviews Chemistry, 4, 674–695, 10.1038/s41570-020-00223-8, 2020. · DOI
  17. Corbett, K. M., Ford, L., Warren, D. B., Pouton, C. W., and Chalmers, D. K.: Cyclosporin Structure and Permeability: From A to Z and Beyond, J. Med. Chem., 64, 13131–13151, 10.1021/acs.jmedchem.1c00580, 2021. · DOI
  18. Craveur, P., Rebehmed, J., and de Brevern, A. G.: PTM-SD: a database of structurally resolved and annotated posttranslational modifications in proteins, Database-Oxford, 2014, bau041, 10.1093/database/bau041, 2014. · DOI
  19. de Araujo, A. D., Lim, J., Wu, K. C., Hoang, H. N., Nguyen, H. T., and Fairlie, D. P.: Landscaping macrocyclic peptides: stapling hDM2-binding peptides for helicity, protein affinity, proteolytic stability and cell uptake, RSC Chem. Biol., 3, 895–904, 10.1039/d1cb00231g, 2022. · DOI
  20. Gfeller, D., Michielin, O., and Zoete, V.: SwissSidechain: a molecular and structural database of non-natural sidechains, Nucleic Acids Res., 41, D327–332, 10.1093/nar/gks991, 2013. · DOI
  21. Goodrich, A. C. and Frueh, D. P.: A nuclear magnetic resonance method for probing molecular influences of substrate loading in nonribosomal peptide synthetase carrier proteins, Biochemistry, 54, 1154–1156, 10.1021/bi501433r, 2015. · DOI
  22. Goto, Y. and Suga, H.: The RaPID Platform for the Discovery of Pseudo-Natural Macrocyclic Peptides, Accounts Chem. Res., 54, 3604–3617, 10.1021/acs.accounts.1c00391, 2021. · DOI
  23. Guntert, P. and Buchner, L.: Combined automated NOE assignment and structure calculation with CYANA, J. Biomol. NMR, 62, 453–471, 10.1007/s10858-015-9924-9, 2015. · DOI
  24. Guntert, P., Mumenthaler, C., and Wuthrich, K.: Torsion angle dynamics for NMR structure calculation with the new program DYANA, J. Mol. Biol., 273, 283–298, 10.1006/jmbi.1997.1284, 1997. · DOI
  25. Hamada, T., Matsunaga, S., Fujiwara, M., Fujita, K., Hirota, H., Schmucki, R., Guntert, P., and Fusetani, N.: Solution structure of polytheonamide B, a highly cytotoxic nonribosomal polypeptide from marine sponge, J. Am. Chem. Soc., 132, 12941–12945, 10.1021/ja104616z, 2010. · DOI
  26. Hoesl, M. G. and Budisa, N.: In vivo incorporation of multiple noncanonical amino acids into proteins, Angew. Chem. Int. Edit., 50, 2896–2902, 10.1002/anie.201005680, 2011. · DOI
  27. Hoyt, E. A., Cal, P. M. S. D., Oliveira, B. L., and Bernardes, G. J. L.: Contemporary approaches to site-selective protein modification, Nature Reviews Chemistry, 3, 147–171, 10.1038/s41570-019-0079-1, 2019. · DOI
  28. Huang, Y., Russell, W. K., Wan, W., Pai, P. J., Russell, D. H., and Liu, W.: A convenient method for genetic incorporation of multiple noncanonical amino acids into one protein in Escherichia coli, Mol. Biosyst., 6, 683–686, 10.1039/b920120c, 2010. · DOI
  29. IUPAC, Division of chemical nomenclature and structure representation: Specification of Configuration and Conformation, in: Nomenclature of Organic Chemistry, edited by: Favre, H. A. and Powell, W. H., The Royal Society of Chemistry, 10.1039/9781849733069-01156, 2013. · DOI
  30. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN): Nomenclature and symbolism for amino acids and peptides. Recommendations 1983, Biochem. J., 219, 345–373, 10.1042/bj2190345, 1984. · DOI
  31. Johnson, J. A., Lu, Y. Y., Van Deventer, J. A., and Tirrell, D. A.: Residue-specific incorporation of non-canonical amino acids into proteins: recent developments and applications, Curr. Opin. Chem. Biol., 14, 774–780, 10.1016/j.cbpa.2010.09.013, 2010. · DOI
  32. Koziara, K. B., Stroet, M., Malde, A. K., and Mark, A. E.: Testing and validation of the Automated Topology Builder (ATB) version 2.0: prediction of hydration free enthalpies, J. Comput. Aid. Mol. Des., 28, 221–233, 10.1007/s10822-014-9713-7, 2014. · DOI
  33. Lee, W., Rahimi, M., Lee, Y., and Chiu, A.: POKY: a software suite for multidimensional NMR and 3D structure calculation of biomolecules, Bioinformatics, 37, 3041–3042, 10.1093/bioinformatics/btab180, 2021. · DOI
  34. Liu, C. C. and Schultz, P. G.: Adding new chemistries to the genetic code, Annu. Rev. Biochem., 79, 413–444, 10.1146/annurev.biochem.052308.105824, 2010. · DOI · Paper page
  35. Loll, P. J., Upton, E. C., Nahoum, V., Economou, N. J., and Cocklin, S.: The high resolution structure of tyrocidine A reveals an amphipathic dimer, Biochim. Biophys. Acta, 1838, 1199–1207, 10.1016/j.bbamem.2014.01.033, 2014. · DOI
  36. Mal, T. K., Bagby, S., and Ikura, M.: Protein structure calculation from NMR data, Methods Mol. Biol., 173, 267–283, 10.1385/1-59259-184-1:267, 2002. · DOI
  37. Malde, A. K., Zuo, L., Breeze, M., Stroet, M., Poger, D., Nair, P. C., Oostenbrink, C., and Mark, A. E.: An Automated Force Field Topology Builder (ATB) and Repository: Version 1.0, J. Chem. Theory Comput., 7, 4026–4037, 10.1021/ct200196m, 2011. · DOI
  38. Marahiel, M. A.: Working outside the protein-synthesis rules: insights into non-ribosomal peptide synthesis, J. Pept. Sci., 15, 799–807, 10.1002/psc.1183, 2009. · DOI
  39. Mareuil, F., Malliavin, T. E., Nilges, M., and Bardiaux, B.: Improved reliability, accuracy and quality in automated NMR structure calculation with ARIA, J. Biomol. NMR, 62, 425–438, 10.1007/s10858-015-9928-5, 2015. · DOI
  40. Markley, J. L., Bax, A., Arata, Y., Hilbers, C. W., Kaptein, R., Sykes, B. D., Wright, P. E., and Wuthrich, K.: Recommendations for the presentation of NMR structures of proteins and nucleic acids. IUPAC-IUBMB-IUPAB Inter-Union Task Group on the Standardization of Data Bases of Protein and Nucleic Acid Structures Determined by NMR Spectroscopy, J. Biomol. NMR, 12, 1–23, 10.1023/a:1008290618449, 1998. · DOI
  41. Martínez-Núñez, M. A. and López, V. E. L. y.: Nonribosomal peptides synthetases and their applications in industry, Sustainable Chemical Processes, 4, 13, 10.1186/s40508-016-0057-6, 2016. · DOI
  42. Mekkattu Tharayil, S., Mahawaththa, M. C., Feintuch, A., Maleckis, A., Ullrich, S., Morewood, R., Maxwell, M. J., Huber, T., Nitsche, C., Goldfarb, D., and Otting, G.: Site-selective generation of lanthanoid binding sites on proteins using 4-fluoro-2,6-dicyanopyridine, Magn. Reson., 3, 169–182, 10.5194/mr-3-169-2022, 2022. · DOI
  43. Mendive-Tapia, L., Preciado, S., Garcia, J., Ramon, R., Kielland, N., Albericio, F., and Lavilla, R.: New peptide architectures through C-H activation stapling between tryptophan-phenylalanine/tyrosine residues, Nat. Commun., 6, 7160, 10.1038/ncomms8160, 2015. · DOI
  44. Noren, C. J., Anthonycahill, S. J., Griffith, M. C., and Schultz, P. G.: A General-Method for Site-Specific Incorporation of Unnatural Amino-Acids into Proteins, Science, 244, 182–188, 10.1126/science.2649980, 1989. · DOI · Paper page
  45. Ramanujam, V., Shen, Y., Ying, J., and Mobli, M.: Residual Dipolar Couplings for Resolving Cysteine Bridges in Disulfide-Rich Peptides, Front. Chem., 7, 889, 10.3389/fchem.2019.00889, 2019. · DOI
  46. Schafer, M., Schneider, T. R., and Sheldrick, G. M.: Crystal structure of vancomycin, Structure, 4, 1509–1515, 10.1016/s0969-2126(96)00156-6, 1996. · DOI
  47. Schmid, N., Christ, C. D., Christen, M., Eichenberger, A. P., and van Gunsteren, W. F.: Architecture, implementation and parallelisation of the GROMOS software for biomolecular simulation, Comput. Phys. Commun., 183, 890–903, 10.1016/j.cpc.2011.12.014, 2012. · DOI
  48. Schwieters, C. D., Kuszewski, J. J., Tjandra, N., and Clore, G. M.: The Xplor-NIH NMR molecular structure determination package, J. Magn. Reson., 160, 65–73, 10.1016/s1090-7807(02)00014-9, 2003. · DOI
  49. Schwieters, C. D., Kuszewski, J. J., and Clore, G. M.: Using Xplor-NIH for NMR molecular structure determination, Prog. Nucl. Mag. Res. Sp., 48, 47–62, 10.1016/j.pnmrs.2005.10.001, 2006. · DOI
  50. Shen, Y. and Bax, A.: Protein backbone and sidechain torsion angles predicted from NMR chemical shifts using artificial neural networks, J. Biomolecular NMR, 56, 227–241, 10.1007/s10858-013-9741-y, 2013. · DOI
  51. Skinner, S. P., Fogh, R. H., Boucher, W., Ragan, T. J., Mureddu, L. G., and Vuister, G. W.: CcpNmr AnalysisAssign: a flexible platform for integrated NMR analysis, J. Biomol. NMR, 66, 111–124, 10.1007/s10858-016-0060-y, 2016. · DOI
  52. Strieker, M., Tanovic, A., and Marahiel, M. A.: Nonribosomal peptide synthetases: structures and dynamics, Curr. Opin. Struc. Biol., 20, 234–240, 10.1016/j.sbi.2010.01.009, 2010. · DOI
  53. Stroet, M., Caron, B., Visscher, K. M., Geerke, D. P., Malde, A. K., and Mark, A. E.: Automated Topology Builder Version 3.0: Prediction of Solvation Free Enthalpies in Water and Hexane, J. Chem. Theory Comput., 14, 5834–5845, 10.1021/acs.jctc.8b00768, 2018. · DOI
  54. Tharp, J. M., Krahn, N., Varshney, U., and Soll, D.: Hijacking Translation Initiation for Synthetic Biology, Chembiochem, 21, 1387–1396, 10.1002/cbic.202000017, 2020. · DOI
  55. Thompson, R. E. and Muir, T. W.: Chemoenzymatic Semisynthesis of Proteins, Chem. Rev., 120, 3051–3126, 10.1021/acs.chemrev.9b00450, 2020. · DOI
  56. Umstatter, F., Domhan, C., Hertlein, T., Ohlsen, K., Muhlberg, E., Kleist, C., Zimmermann, S., Beijer, B., Klika, K. D., Haberkorn, U., Mier, W., and Uhl, P.: Vancomycin Resistance Is Overcome by Conjugation of Polycationic Peptides, Angew. Chem. Int. Edit., 59, 8823–8827, 10.1002/anie.202002727, 2020. · DOI
  57. Van Der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A. E., and Berendsen, H. J.: GROMACS: fast, flexible, and free, J. Comput. Chem., 26, 1701–1718, 10.1002/jcc.20291, 2005. · DOI
  58. Vranken, W. F., Boucher, W., Stevens, T. J., Fogh, R. H., Pajon, A., Llinas, M., Ulrich, E. L., Markley, J. L., Ionides, J., and Laue, E. D.: The CCPN data model for NMR spectroscopy: development of a software pipeline, Proteins, 59, 687–696, 10.1002/prot.20449, 2005. · DOI
  59. Walsh, C. T., Garneau-Tsodikova, S., and Gatto Jr., G. J.: Protein posttranslational modifications: the chemistry of proteome diversifications, Angew. Chem. Int. Edit., 44, 7342–7372, 10.1002/anie.200501023, 2005. · DOI
  60. Wang, J., Wang, W., Kollman, P. A., and Case, D. A.: Automatic atom type and bond type perception in molecular mechanical calculations, J. Mol. Graph. Model., 25, 247–260, 10.1016/j.jmgm.2005.12.005, 2006. · DOI
  61. Wang, L., Brock, A., Herberich, B., and Schultz, P. G.: Expanding the genetic code of Escherichia coli, Science, 292, 498–500, 10.1126/science.1060077, 2001. · DOI
  62. Wang, T., Liang, C., An, Y., Xiao, S., Xu, H., Zheng, M., Liu, L., Wang, G., and Nie, L.: Engineering the Translational Machinery for Biotechnology Applications, Mol. Biotechnol., 62, 219–227, 10.1007/s12033-020-00246-y, 2020. · DOI
  63. Weber, C., Wider, G., von Freyberg, B., Traber, R., Braun, W., Widmer, H., and Wuthrich, K.: The NMR structure of cyclosporin A bound to cyclophilin in aqueous solution, Biochemistry, 30, 6563–6574, 10.1021/bi00240a029, 1991. · DOI
  64. Westbrook, J. D., Shao, C., Feng, Z., Zhuravleva, M., Velankar, S., and Young, J.: The chemical component dictionary: complete descriptions of constituent molecules in experimentally determined 3D macromolecules in the Protein Data Bank, Bioinformatics, 31, 1274–1278, 10.1093/bioinformatics/btu789, 2015. · DOI
  65. Wu, Y., Li, Y. H., Li, X., Zou, Y., Liao, H. L., Liu, L., Chen, Y. G., Bierer, D., and Hu, H. G.: A novel peptide stapling strategy enables the retention of ring-closing amino acid side chains for the Wnt/beta-catenin signalling pathway, Chem. Sci., 8, 7368–7373, 10.1039/c7sc02420g, 2017. · DOI
  66. Yilmaz, E. M. and Guntert, P.: NMR structure calculation for all small molecule ligands and non-standard residues from the PDB Chemical Component Dictionary, J. Biomol. NMR, 63, 21–37, 10.1007/s10858-015-9959-y, 2015. · DOI
  67. Zou, H., Li, L., Zhang, T., Shi, M., Zhang, N., Huang, J., and Xian, M.: Biosynthesis and biotechnological application of non-canonical amino acids: Complex and unclear, Biotechnol. Adv., 36, 1917–1927, 10.1016/j.biotechadv.2018.07.008, 2018. · DOI

Metadata

Authors
Kuschert, S., Stroet, M., Chin, Y. K.-Y., Conibear, A. C., Jia, X., Lee, T., Bartling, C. R. O., Strømgaard, K., Güntert, P., Rosengren, K. J., Mark, A. E., & Mobli, M.
Affiliations
  • The University of Queensland (AU)
  • TU Wien (AT)
  • University of Copenhagen (DK)
  • Goethe University Frankfurt (DE)
Corresponding author
Mobli, Mehdi
ORCID
Venue
Magnetic Resonance
Publisher
Copernicus GmbH
Published
2023-02-24
Volume
4
Issue
1
Pages
57-72
ISSN
2699-0016 (ISSN-L)
DOI
10.5194/mr-4-57-2023
PMC
PMC10583272
OpenAlex
W4321784268
Cited by
9
References
2
Citations by year
2026: 2 · 2025: 1 · 2024: 2 · 2023: 4
FWCI
0.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Magnetic Resonance (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
  • ETH Zürich Research Collection
Funders
  • Australian Research Council (DP190101177, DP220103028, DP220100896)
  • Austrian Science Fund (P36101-B)
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced NMR Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
Keywords
unnatural amino acids, NMR structure determination, Cyana, structural templates, vancomycin, synthetic peptides, protein chemical modification

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