Abstract
Sortases are Gram-positive bacterial extracellular transpeptidases involved in the attachment of surface proteins to the cell wall. The mechanism of action of Staphylococcus aureus Sortase A (SrtA) is based on specific recognition of the LPXTG motive at the C-terminus of the surface protein, cleavage of this site between threonine and glycine residues, subsequent transfer of the N-terminal transmembrane domain to the amino group of the pentaglycine linker and thus anchoring of proteins with this motive on the cell surface. As SrtA is involved in both early and late stages of bacterial infection because it attaches adhesins and immune evasion proteins to the cell wall, this enzyme is a good target for combating bacterial infections. The oligopeptide LPRDA was recently found to be an effective inhibitor of the enzymatic activity of SrtA through competitive binding to its active site. By NMR spectroscopy we solved the solution structure of the LPRDA peptide and showed the presence of several conformers in solution. The obtained data are the basis for further studies of the structure and function of peptidomimetics based on LPRDA oligopeptide.
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References
M. Terreni, M. Taccani, M. Pregnolato, Molecules 26, 2671 (2021)
V. Singh, K. Chibale, Acc. Chem. Res. 54, 2361–2376 (2021)
D. Joh, E.R. Wann, B. Kreikemeyer, P. Speziale, M. Höök, Matrix Biol. 18, 211–223 (1999)
C. Heilmann, Adv. Exp. Med. Biol. 715, 105–123 (2011)
T.J. Foster, Microbiol. Spectr. 7, 1–22 (2019)
N. Suree, M.E. Jung, R.T. Clubb, Mini Rev. Med. Chem. 7, 991–1000 (2007)
H. Abujubara, J.C.J. Hintzen, S. Rahimi, I. Mijakovic, D. Tietze, A.A. Tietze, Chem. Sci. 14, 6975–6985 (2023)
K.W. Clancy, J.A. Melvin, D.G. McCafferty, Biopolymers 94, 385–396 (2010)
U. Ilangovan, H. Ton-That, J. Iwahara, O. Schneewind, R.T. Clubb, Proc. Natl. Acad. Sci. U. S. A. 98, 6056–6061 (2001)
D.A. Johnson, I.M. Piper, B.A. Vogel, S.N. Jackson, J.E. Svendsen, H.M. Kodama, D.E. Lee, K.M. Lindblom, J. McCarty, J.M. Antos, J.F. Amacher, J. Biol. Chem. 298, 102446 (2022)
N. Suree, C.K. Liew, V.A. Villareal, W. Thieu, E.A. Fadeev, J.J. Clemens, M.E. Jung, R.T. Clubb, J. Biol. Chem. 284, 24465–24477 (2009)
K.H. Jang, S.C. Chung, J. Shin, S.H. Lee, T.I. Kim, H.S. Lee, K.B. Oh, Bioorg. Med. Chem. Lett. 17, 5366–5369 (2007)
K.B. Oh, W. Mar, S. Kim, J.Y. Kim, M.N. Oh, J.G. Kim, D. Shin, C.J. Sim, J. Shin. Bioorg. Med. Chem. Lett. 15, 4927–4931 (2005)
B.A. Frankel, M. Bentley, R.G. Kruger, D.G. McCafferty, J. Am. Chem. Soc. 126, 3404–3405 (2004)
K.B. Oh, S.H. Kim, J. Lee, W.J. Cho, T. Lee, S. Kim, J. Med. Chem. 47, 2418–2421 (2004)
K.V. Kudryavtsev, M.L. Bentley, D.G. McCafferty, Bioorg. Med. Chem. 17, 2886–2893 (2009)
J. Zhang, H. Liu, K. Zhu, S. Gong, S. Dramsi, Y.T. Wang, J. Li, F. Chen, R. Zhang, L. Zhou, L. Lan, H. Jiang, O. Schneewind, C. Luo, C.G. Yang, Proc. Natl. Acad. Sci. U. S. A. 111, 13517–13522 (2014)
D. Zhulenkovs, Z. Rudevica, K. Jaudzems, M. Turks, A. Leonchiks, Bioorg. Med. Chem. 22, 5988–6003 (2014)
K. Jaudzems, V. Kurbatska, A. Je Kabsons, R. Bobrovs, Z. Rudevica, A. Leonchiks, ACS Infect Dis. 6, 186–194 (2020)
J. Wang, H. Li, J. Pan, J. Dong, X. Zhou, X. Niu, X. Deng, Front. Microbiol. 9, 245 (2018)
S.A. Bozhkova, E.M. Gordina, D.V. Labutin, K.V. Kudryavtsev, Antibiotics 11, 1836 (2022)
D.A. Shulga, K.V. Kudryavtsev, Molecules 27, 8182 (2022)
I. Coin, M. Beyermann, M. Bienert, Nat. Protoc. 2, 3247–3256 (2007)
M. Liu, X. Mao, C. He, H. Huang, J.K. Nicholson, J.C. Lindon, J. Magn. Reson. 132, 125–129 (1998)
M. Piotto, V. Saudek, V. Sklenar, J. Biomol. NMR 2, 661 (1992)
T.L. Hwang, A.J. Shaka, J. Magn. Reson. 112, 275–279 (1995)
A.G. Palmer III., J. Cavanagh, P.E. Wright, M. Rance, J. Magn. Reson. 93, 151–170 (1991)
G. Bodenhausen, D., J. Ruben. Chem. Phys. Lett. 69, 185–189 (1980)
W.F. Vranken, W. Boucher, T.J. Stevens, R.H. Fogh, A. Pajon, M. Llinas, E.L. Ulrich, J.L. Markley, J. Ionides, E.D. Laue, Proteins 59, 687–696 (2005)
B. Bardiaux, T. Malliavin, M. Nilges, Methods Mol. Biol. 831, 453–483 (2012)
C.J. Williams, J.J. Headd, N.W. Moriarty, M.G. Prisant, L.L. Videau, L.N. Deis, V. Verma, D.A. Keedy, B.J. Hintze, V.B. Chen, S. Jain, S.M. Lewis, W.B. Arendall 3rd., J. Snoeyink, P.D. Adams, S.C. Lovell, J.S. Richardson, D.C. Richardson, Protein Sci. 27, 293–315 (2018)
E.F. Pettersen, T.D. Goddard, C.C. Huang, E.C. Meng, G.S. Couch, T.I. Croll, J.H. Morris, T.E. Ferrin, Protein Sci. 30, 70–82 (2021)
Sh. Yang, F. Delaglio, G. Cornilescu, A. Bax, J. Biomol. NMR 44, 213–223 (2009)
D.S. Blokhin, S.V. Efimov, A.V. Klochkov, A.R. Yulmetov, A.V. Filippov, O.N. Antzutkin, A.V. Aganov, V.V. Klochkov, Appl. Magn. Reson. 41, 267–282 (2011)
Acknowledgements
NMR spectra acquisition was financially supported by the subsidy allocated to Kazan Federal University for the state assignment in the sphere of scientific activities (project FZSM-2023-0012). NMR data analysis and molecular dynamic calculations were supported by the government assignment for FRC Kazan Scientific Center of RAS (121110200038-7). Synthesis and purification of LPRDA were supported by the Russian Science Foundation, grant # 20-15-00258.
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All authors contributed to the study conception and design. Conceptualization: KVK and KSU; methodology: ESK.; software: ESV; validation: AVK and KSU; formal analysis: ESK and AVA; investigation: ESK, PMI, KVK. and KSU.; resources: AVA.; data curation: ESK, SVE, AVK and KSU; writing original draft preparation: ESK.; writing review and editing: KVK and KSU; visualization: ESK and KSU; supervision: KVK. and KSU; project administration: KSU; funding acquisition: KSU and KVK. All authors read and approved the final manuscript.
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Kuchaev, E.S., Efimov, S.V., Klochkov, A.V. et al. Solution NMR Studies of LPRDA Peptide: an Oligopeptide Inhibitor of Staphylococcus aureus Sortase A. Appl Magn Reson 55, 451–461 (2024). https://doi.org/10.1007/s00723-023-01635-7
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DOI: https://doi.org/10.1007/s00723-023-01635-7