A molecular mechanism for the enzymatic methylation of nitrogen atoms within peptide bonds

Science Advances

Volumn 4, Issue 8, 2018, Pages

  Song, Haigang ^a,b   Van Der Velden, Niels S ^c   Shiran, Sally L ^a   Bleiziffer, Patrick ^c   Zach, Christina ^c   Sieber, Ramon ^c   Imani, Aman S ^d   Krausbeck, Florian ^c   Aebi, Markus ^c   Freeman, Michael F ^d   Riniker, Sereina ^c   Künzler, Markus ^c   Naismith, James H ^b,e,f  

^a UNIVERSITY OF ST ANDREWS   (United Kingdom)

^b WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^c ETH ZURICH   (Switzerland)

^d UNIVERSITY OF MINNESOTA   (United States)

^e SICHUAN UNIVERSITY   (China)

^f RUTHERFORD APPLETON LABORATORY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALKYLATION; AMIDES; AMINO ACIDS; METHYLATION; REACTION INTERMEDIATES;

BASE-CATALYZED REACTION; CHEMICAL METHYLATIONS; COMPUTATIONAL MODEL; MEDICINAL CHEMISTRY; MEMBRANE PERMEABILITY; MOLECULAR MECHANISM; NUCLEOPHILIC ATTACK; S-ADENOSYL METHIONINES;

PEPTIDES;

AMIDE; METHYLTRANSFERASE; NITROGEN; PEPTIDE FRAGMENT; S ADENOSYLHOMOCYSTEINE; S ADENOSYLMETHIONINE;

CATALYSIS; CHEMISTRY; ELECTRON; METABOLISM; METHYLATION; PROTEIN CONFORMATION; X RAY CRYSTALLOGRAPHY;

AMIDES; CATALYSIS; CRYSTALLOGRAPHY, X-RAY; ELECTRONS; METHYLATION; METHYLTRANSFERASES; NITROGEN; PEPTIDE FRAGMENTS; PROTEIN CONFORMATION; S-ADENOSYLHOMOCYSTEINE; S-ADENOSYLMETHIONINE;

EID: 85052239215     PISSN: None     EISSN: 23752548     Source Type: Journal    
DOI: 10.1126/sciadv.aat2720     Document Type: Article

References (75)

1. G. Scherer, M. L. Kramer, M. Schutkowski, U. Reimer, G. Fischer, Barriers to rotation of secondary amide peptide bonds. J. Am. Chem. Soc. 120, 5568–5574 (1998).
2. F. G. Bordwell, J. A. Harrelson Jr., T. Y. Lynch, Homolytic bond dissociation energies for the cleavage of .alpha.-nitrogen-hydrogen bonds in carboxamides, sulfonamides, and their derivatives. The question of synergism in nitrogen-centered radicals. J. Org. Chem. 55, 3337–3341 (1990).
3. C. T. Walsh, H. Chen, T. A. Keating, B. K. Hubbard, H. C. Losey, L. Luo, C. G. Marshall, D. A. Miller, H. M. Patel, Tailoring enzymes that modify nonribosomal peptides during and after chain elongation on NRPS assembly lines. Curr. Opin. Chem. Biol. 5, 525–534 (2001).
4. W. Ding, W.-Q. Liu, Y. Jia, Y. Li, W. A. van der Donk, Q. Zhang, Biosynthetic investigation of phomopsins reveals a widespread pathway for ribosomal natural products in ascomycetes. Proc. Natl. Acad. Sci. U.S.A. 113, 3521–3526 (2016).
5. N. Nagano, M. Umemura, M. Izumikawa, J. Kawano, T. Ishii, M. Kikuchi, K. Tomii, T. Kumagai, A. Yoshimi, M. Machida, K. Abe, K. Shin-ya, K. Asai, Class of cyclic ribosomal peptide synthetic genes in filamentous fungi. Fungal Genet. Biol. 86, 58–70 (2016).
6. M. Z. Ansari, J. Sharma, R. S. Gokhale, D. Mohanty, In silico analysis of methyltransferase domains involved in biosynthesis of secondary metabolites. BMC Bioinformatics 9, 454 (2008).
7. M. Teixidó, F. Albericio, E. Giralt, Solid‐phase synthesis and characterization of N‐methyl‐rich peptides. J. Pept. Res. 65, 153–166 (2005).
8. A. T. Bockus, J. A. Schwochert, C. R. Pye, C. E. Townsend, V. Sok, M. A. Bednarek, R. S. Lokey, Going out on a limb: Delineating the effects of -branching, N-methylation, and side chain size on the passive permeability, solubility, and flexibility of sanguinamide A analogues. J. Med. Chem. 58, 7409–7418 (2015).
9. A. T. Bockus, K. W. Lexa, C. R. Pye, A. S. Kalgutkar, J. W. Gardner, K. C. R. Hund, W. M. Hewitt, J. A. Schwochert, E. Glassey, D. A. Price, A. M. Mathiowetz, S. Liras, M. P. Jacobson, R. Scott Lokey, Probing the physicochemical boundaries of cell permeability and oral bioavailability in lipophilic macrocycles inspired by natural products. J. Med. Chem. 58, 4581–4589 (2015).
10. P. Matsson, B. C. Doak, B. Over, J. Kihlberg, Cell permeability beyond the rule of 5. Adv. Drug Deliv. Rev. 101, 42–61 (2016).
11. A. Mayer, H. Anke, O. Sterner, Omphalotin, a new cyclic peptide with potent nematicidal activity from Omphalotus olearius I. fermentation and biological activity. Nat. Prod. Lett. 10, 25–32 (1997).
12. N. S. van der Velden, N. Kälin, M. J. Helf, J. Piel, M. F. Freeman, M. Künzler, Autocatalytic backbone N-methylation in a family of ribosomal peptide natural products. Nat. Chem. Biol. 13, 833–835 (2017).
13. S. Ramm, B. Krawczyk, A. Mühlenweg, A. Poch, E. Mösker, R. D. Süssmuth, A self‐sacrificing N‐methyltransferase is the precursor of the fungal natural product omphalotin. Angew. Chem. Int. Ed. Engl. 56, 9994–9997 (2017).
14. F. Schwarz, M. Aebi, Mechanisms and principles of N-linked protein glycosylation. Curr. Opin. Struct. Biol. 21, 576–582 (2011).
15. C. Lizak, S. Gerber, S. Numao, M. Aebi, K. P. Locher, X-ray structure of a bacterial oligosaccharyltransferase. Nature 474, 350–355 (2011).
16. C. Lizak, S. Gerber, G. Michaud, M. Schubert, Y.-Y. Fan, M. Bucher, T. Darbre, M. Aebi, J.-L. Reymond, K. P. Locher, Unexpected reactivity and mechanism of carboxamide activation in bacterial N-linked protein glycosylation. Nat. Commun. 4, 2627 (2013).
17. Y. Wu, Q. Kang, G. Shang, P. Spiteller, B. Carroll, T.-W. Yu, W. Su, L. Bai, H. G. Floss, N‐methylation of the amide bond by methyltransferase asm10 in ansamitocin biosynthesis. Chembiochem 12, 1759–1766 (2011).
18. J. Vévodová, R. M. Graham, E. Raux, H. L. Schubert, D. I. Roper, A. A. Brindley, A. Ian Scott, C. A. Roessner, N. P. Stamford, M. Elizabeth Stroupe, E. D. Getzoff, M. J. Warren, K. S. Wilson, Structure/function studies on a S-adenosyl-l-methionine-dependent uroporphyrinogen III C methyltransferase (SUMT), a key regulatory enzyme of tetrapyrrole biosynthesis. J. Mol. Biol. 344, 419–433 (2004).
19. S. Storbeck, S. Saha, J. Krausze, B. U. Klink, D. W. Heinz, G. Layer, Crystal structure of the heme d1 biosynthesis enzyme NirE in complex with its substrate reveals new insights into the catalytic mechanism of S-adenosyl-L-methionine-dependent uroporphyrinogen III methyltransferases. J. Biol. Chem. 286, 26754–26767 (2011).
20. B. J. G. E. Pieters, M. B. van Eldijk, R. J. M. Nolte, J. Mecinović, Natural supramolecular protein assemblies. Chem. Soc. Rev. 45, 24–39 (2016).
21. M. Oke, M. Kerou, H. Liu, X. Peng, R. A. Garrett, D. Prangishvili, J. H. Naismith, M. F. White, A dimeric rep protein initiates replication of a linear archaeal virus genome: implications for the rep mechanism and viral replication. J. Virol. 85, 925–931 (2011).
22. A. Jansson, H. Koskiniemi, P. Mäntsälä, J. Niemi, G. Schneider, Crystal structure of a ternary complex of DnrK, a methyltransferase in daunorubicin biosynthesis, with bound products. J. Biol. Chem. 279, 41149–41156 (2004).
23. C. J. Dong, F. Huang, H. Deng, C. Schaffrath, J. B. Spencer, D. O’Hagan, J. H. Naismith, Crystal structure and mechanism of a bacterial fluorinating enzyme. Nature 427, 561–565 (2004).
24. X. Zhu, D. A. Robinson, A. R. McEwan, D. O’Hagan, J. H. Naismith, Mechanism of enzymatic fluorination in Streptomyces cattleya. J. Am. Chem. Soc. 129, 14597–14604 (2007).
25. J. P. Klinman, Enzyme dynamics: Control of active-site compression. Nat. Chem. 2, 907–909 (2010).
26. C. L. Perrin, Proton exchange in amides: Surprises from simple systems. Acc. Chem. Res. 22, 268–275 (1989).
27. T. J. Donohoe, C. J. R. Bataille, P. Innocenti, Hydrogen‐bonding‐mediated directed osmium dihydroxylation. Organic Reactions (2012).
28. Y. Liu, J. B. Thoden, J. Kim, E. Berger, A. M. Gulick, F. J. Ruzicka, H. M. Holden, P. A. Frey, Mechanistic roles of tyrosine 149 and serine 124 in UDP-galactose 4-epimerase from Escherichia coli. Biochemistry 36, 10675–10684 (1997).
29. A. Nakamura, T. Ishida, K. Kusaka, T. Yamada, S. Fushinobu, I. Tanaka, S. Kaneko, K. Ohta, H. Tanaka, K. Inaka, Y. Higuchi, N. Niimura, M. Samejima, K. Igarashi, “Newton’s cradle” proton relay with amide–imidic acid tautomerization in inverting cellulase visualized by neutron crystallography. Sci. Adv. 1, e1500263 (2015).
30. J. Gao, S. Ma, D. T. Major, K. Nam, J. Pu, D. G. Truhlar, Mechanisms and free energies of enzymatic reactions. Chem. Rev. 106, 3188–3209 (2006).
31. J. Lameira, R. P. Bora, Z. T. Chu, A. Warshel, Methyltransferases do not work by compression, cratic, or desolvation effects, but by electrostatic preorganization. Proteins 83, 318–330 (2015).
32. H. Liu, J. H. Naismith, An efficient one-step site-directed deletion, insertion, single and multiple-site plasmid mutagenesis protocol. BMC Biotechnol. 8, 91 (2008).
33. P. Evans, Scaling and assessment of data quality. Acta Crystallogr. D Biol. Crystallogr. 62, 72–82 (2006).
34. P. R. Evans, G. N. Murshudov, How good are my data and what is the resolution? Acta Crystallogr. D Biol. Crystallogr. 69, 1204–1214 (2013).
35. W. Kabsch, Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants. J. Appl. Cryst. 26, 795–800 (1993).
36. G. Winter, xia2: An expert system for macromolecular crystallography data reduction. J. Appl. Cryst. 43, 186–190 (2009).
37. C. Vonrhein, C. Flensburg, P. Keller, A. Sharff, O. Smart, W. Paciorek, T. Womack, G. Bricognea, Data processing and analysis with the autoPROC toolbox. Acta Crystallogr. D Biol. Crystallogr. 67, 293–302 (2011).
38. M. D. Winn, C. C. Ballard, K. D. Cowtan, E. J. Dodson, P. Emsley, P. R. Evans, R. M. Keegan, E. B. Krissinel, A. G. W. Leslie, A. McCoy, S. J. McNicholas, G. N. Murshudov, N. S. Pannu, E. A. Potterton, H. R. Powell, R. J. Read, A. Vagin, K. S. Wilson, Overview of the CCP4 suite and current developments. Acta Crystallogr. D Biol. Crystallogr. 67, 235–242 (2011).
39. W. Minor, M. Cymborowski, Z. Otwinowski, Automatic system for crystallographic data collection and analysis. Acta Phys. Pol., A 101, 613–619 (2002).
40. Collaborative Computational Project, Number 4, The CCP4 suite: Programs for protein crystallography. Acta Crystallogr. D Biol. Crystallogr. 50, 760–763 (1994).
41. P. Skubák, N. S. Pannu, Automatic protein structure solution from weak x-ray data. Nat. Commun. 4, 2777 (2013).
42. P. Emsley, K. Cowtan, Coot: Model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126–2132 (2004).
43. G. N. Murshudov, P. Skubák, A. A. Lebedev, N. S. Pannu, R. A. Steiner, R. A. Nicholls, M. D. Winn, F. Long, A. A. Vagin, REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr. D Biol. Crystallogr. 67, 355–367 (2011).
44. P. D. Adams, K. Gopal, R. W. Grosse-Kunstleve, L.-W. Hung, T. R. Ioerger, A. J. McCoy, N. W. Moriarty, R. K. Pai, R. J. Read, T. D. Romo, J. C. Sacchettini, N. K. Sauter, L. C. Storoni, T. C. Terwilliger, Recent developments in the PHENIX software for automated crystallographic structure determination. J. Synchrotron Radiat. 11, 53–55 (2004).
45. A. J. McCoy, A. J. McCoy, R. W. Grosse-Kunstleve, P. D. Adams, M. D. Winn, L. C. Storoni, R. J. Read, Phaser crystallographic software. J. Appl. Crystallogr. 40, 658–674 (2007).
46. I. W. Davis, A. Leaver-Fay, V. B. Chen, J. N. Block, G. J. Kapral, X. Wang, L. W. Murray, W. Bryan Arendall III, J. Snoeyink, J. S. Richardson, D. C. Richardson, MolProbity: All-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Res. 35, W375–W383 (2007).
47. S. McNicholas, E. Potterton, K. S. Wilson, M. E. M. Noble, Presenting your structures: The CCP4mg molecular-graphics software. Acta Crystallogr. D Biol. Crystallogr. 67, 386–394 (2011).
48. A.-P. E. Kunz, J. R. Allison, D. P. Geerke, B. A. C. Horta, P. H. Hünenberger, S. Riniker, N. Schmid, W. F. van Gunsteren, New functionalities in the GROMOS biomolecular simulation software. J. Comput. Chem. 33, 340–353 (2012).
49. N. Schmid, A. P. Eichenberger, A. Choutko, S. Riniker, M. Winger, A. E. Mark, W. F. van Gunsteren, Definition and testing of the GROMOS force-field versions 54A7 and 54B7. Eur. Biophys. J. 40, 843–856 (2011).
50. K. B. Koziara, M. Stroet, A. K. Malde, A. E. Mark, Testing and validation of the Automated Topology Builder (ATB) version 2.0: Prediction of hydration free enthalpies. J.Comput. Aided Mol. Des. 28, 221 (2014).
51. J.-P. Ryckaert, G. Ciccotti, H. J. C. Berendsen, Numerical integration of the cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. J. Comput. Phys. 23, 327–341 (1977).
52. H. J. C. Berendsen, J. P. M. Postma, W. F. van Gunsteren, A. R. H. J. DiNola, J. R. Haak, Molecular dynamics with coupling to an external bath. J. Chem. Phys. 81, 3684 (1984).
53. R. W. Hockney, The potential calculation and some applications. Methods Comput. Phys. 9, 136–211 (1970).
54. I. G. Tironi, R. Sperb, P. E. Smith, W. F. van Gunsteren, A generalized reaction field method for molecular dynamics simulations. J. Chem. Phys. 102, 5451–5459 (1995).
55. T. N. Heinz, W. F. van Gunsteren, P. H. Hünenberger, Comparison of four methods to compute the dielectric permittivity of liquids from molecular dynamics simulations. J. Chem. Phys. 115, 1125–1136 (2001).
56. A. Fiser, A. Sali, ModLoop: Automated modeling of loops in protein structures. Bioinformatics 19, 2500–2501 (2003).
57. A. P. Eichenberger, J. R. Allison, J. Dolenc, D. P. Geerke, B. A. C. Horta, K. Meier, C. Oostenbrink, N. Schmid, D. Steiner, D. Wang, W. F. van Gunsteren, GROMOS++ software for the analysis of biomolecular simulation trajectories. J. Chem. Theory Comput. 7, 3379–3390 (2011).
58. R. G. Parr, Proceedings of the Third International Congress of Quantum Chemistry, in Horizons of Quantum Chemistry, K. Fukui, B. Pullman, Eds. (D. Reidel Publ. Co., 1981).
59. S. H. Vosko, L. Wilk, M. Nusair, Accurate spin-dependent electron liquid correlation energies for local spin density calculations: A critical analysis. Can. J. Phys. 58, 1200–1211 (1980).
60. A. D. Becke, A new mixing of Hartree–Fock and local density‐functional theories. J. Chem. Phys. 98, 1372–1377 (1993).
61. V. N. Staroverov, G. E. Scuseria, J. Tao, J. P. Perdew, Comparative assessment of a new nonempirical density functional: Molecules and hydrogen-bonded complexes. J. Chem. Phys. 119, 12129–12137 (2003).
62. G. A. Petersson, A. Bennett, T. G. Tensfeldt, M. A. Al-Laham, W. A. Shirley, A complete basis set model chemistry. I. The total energies of closed‐shell atoms and hydrides of the first‐row elements. J. Chem. Phys. 89, 2193–2218 (1988).
63. G. A. Petersson, M. A. Al‐Laham, A complete basis set model chemistry. II. Open‐shell systems and the total energies of the first‐row atoms. J. Chem. Phys. 94, 6081–6090 (1991).
64. M. Milko, J. Noga, Š. Varga, Accuracy of density fitting in calculation of two‐electron repulsion integrals in periodic systems. Int. J. Quan. Chem. 107, 2158–2168 (2007).
65. R. Polly, H.-J. Werner, F. R. Manby, P. J. Knowles, Fast Hartree-Fock theory using local density fitting approximations. Mol. Phys. 102, 2311–2321 (2004).
66. G. Scalmani, M. J. Frisch, Continuous surface charge polarizable continuum models of solvation. I. General formalism. J. Chem. Phys. 132, 114110 (2010).
67. T. Simonson, C. L. Brooks, Charge screening and the dielectric constant of proteins: Insights from molecular dynamics. J. Am. Chem. Soc. 118, 8452–8458 (1996).
68. − . J. Chem. Phys. 66, 2153–2156 (1977).
69. C. Gonzalez, H. B. Schlegel, Reaction path following in mass-weighted internal coordinates. J. Phys. Chem. 94, 5523–5527 (1990).
70. P. Y. Ayala, H. B. Schlegel, A combined method for determining reaction paths, minima, and transition state geometries. J. Chem. Phys. 107, 375–384 (1997).
71. F. Corpet, Multiple sequence alignment with hierarchical clustering. Nucleic Acids Res. 16, 10881–10890 (1988).
72. X. Robert, P. Gouet, Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Res. 42, W320–W324 (2014).
73. T. Hamilton, P. Pulay, Direct inversion in the iterative subspace (DIIS) optimization of open‐shell, excited‐state, and small multiconfiguration SCF wave functions. J. Chem. Phys. 84, 5728–5734 (1986).
74. P. Császár, P. Pulay, Geometry optimization by direct inversion in the iterative subspace. J. Mol. Struct. 114, 31–34 (1984).
75. X. Li, M. J. Frisch, Energy-represented direct inversion in the iterative subspace within a hybrid geometry optimization method. J. Chem. Theory Comput. 2, 835–839 (2006).