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Research Articles

Molecular dynamics simulations reveal the impact of NUDT15 R139C and R139H variants in structural conformation and dynamics

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Pages 14812-14821 | Received 25 Oct 2022, Accepted 22 Feb 2023, Published online: 12 Mar 2023

References

  • Álvarez-Fernández, H., Mingo-Casas, P., Blázquez, A.-B., Caridi, F., Saiz, J. C., Pérez-Pérez, M.-J., Martín-Acebes, M. A., & Priego, E.-M. (2022, November 11). Allosteric inhibition of neutral sphingomyelinase 2 (nSMase2) by DPTIP: From antiflaviviral activity to deciphering its binding site through in silico studies and experimental validation. International Journal of Molecular Sciences, 23(22), 13935. https://doi.org/10.3390/ijms232213935
  • Bauer, P., Hess, B., & Lindahl, E. (2022). GROMACS 2022.3 manual. Zenodo.
  • Belli, M., & Tabocchini, M. A. (2020, August 20). Ionizing radiation-induced epigenetic modifications and their relevance to radiation protection. International Journal of Molecular Sciences, 21(17), 5993. https://doi.org/10.3390/ijms21175993
  • Cargnin, S., Genazzani, A. A., Canonico, P. L., & Terrazzino, S. (2018, September). Diagnostic accuracy of NUDT15 gene variants for thiopurine-induced leukopenia: A systematic review and meta-analysis. Pharmacological Research, 135, 102–111. https://doi.org/10.1016/j.phrs.2018.07.021
  • Carreras-Puigvert, J., Zitnik, M., Jemth, A.-S., Carter, M., Unterlass, J. E., Hallström, B., Loseva, O., Karem, Z., Calderón-Montaño, J. M., Lindskog, C., Edqvist, P.-H., Matuszewski, D. J., Ait Blal, H., Berntsson, R. P. A., Häggblad, M., Martens, U., Studham, M., Lundgren, B., Wählby, C., … Helleday, T. (2017, November 16). A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family. Nature Communications, 8(1), 1541. https://doi.org/10.1038/s41467-017-01642-w
  • Carter, M., Jemth, A.-S., Hagenkort, A., Page, B. D. G., Gustafsson, R., Griese, J. J., Gad, H., Valerie, N. C. K., Desroses, M., Boström, J., Warpman Berglund, U., Helleday, T., & Stenmark, P. (2015, August 4). Crystal structure, biochemical and cellular activities demonstrate separate functions of MTH1 and MTH2. Nature Communications, 6, 7871. https://doi.org/10.1038/ncomms8871
  • David, C. C., & Jacobs, D. J. (2014). Principal component analysis: A method for determining the essential dynamics of proteins. Methods in Molecular Biology (Clifton, N.J.), 1084, 193–226. https://doi.org/10.1007/978-1-62703-658-0_11
  • Essmann, U., L., Perera, M. L., Berkowitz, T., Darden, H., Lee, Lee., & G., Pedersen. (1995, November 15). A smooth particle mesh ewald method. The Journal of Chemical Physics, 103(19), 8577–8593. https://doi.org/10.1063/1.470117
  • García-Marín, J., Griera, M., Alajarín, R., Rodríguez-Puyol, M., Rodríguez-Puyol, D., & Vaquero, J. J. (2021, September 16). A computer-driven scaffold-hopping approach generating new PTP1B inhibitors from the pyrrolo[1,2-a]quinoxaline core. ChemMedChem, 16(18), 2895–2906. https://doi.org/10.1002/cmdc.202100338
  • García-Marín, J., Rodríguez-Puyol, D., & Vaquero, J. J. (2022, August). Insight into the mechanism of molecular recognition between human integrin-linked kinase and Cpd22 and its implication at atomic level. Journal of Computer-Aided Molecular Design, 36(8), 575–589. https://doi.org/10.1007/s10822-022-00466-1
  • Ge, Y., van der Kamp, M., Malaisree, M., Liu, D., Liu, Y., & Mulholland, A. J. (2017, November). Identification of the quinolinedione inhibitor binding site in Cdc25 phosphatase B through docking and molecular dynamics simulations. Journal of Computer-Aided Molecular Design, 31(11), 995–1007. https://doi.org/10.1007/s10822-017-0073-y
  • Goldenberg, O., Erez, E., Nimrod, G., & Ben-Tal, N. (2009, January). The ConSurf-DB: Pre-calculated evolutionary conservation profiles of protein structures. Nucleic Acids Research, 37(suppl_1), D323–D327. https://doi.org/10.1093/nar/gkn822
  • Humphrey, W., Dalke, A., & Schulten, K. (1996). VMD: Visual molecular dynamics. Journal of Molecular Graphics, 14(1), 33–38. https://www.sciencedirect.com/science/article/pii/0263785596000185
  • Hunter, J. D. (2007). Matplotlib: A 2D graphics environment. Computing in Science & Engineering, 9, 96-97. https://doi.org/10.1109/MCSE.2007.55
  • Jo, S., Kim, T., Iyer, V. G., & Im, W. (2008, August). CHARMM-GUI: A web-based graphical user interface for CHARMM. Journal of Computational Chemistry, 29(11), 1859–1865. https://doi.org/10.1002/jcc.20945
  • Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W., & Klein, M. L. (1983, July 15). Comparison of simple potential functions for simulating liquid water. The Journal of Chemical Physics, 79(2), 926–935. https://doi.org/10.1063/1.445869
  • Karran, P., & Attard, N. (2008, January). Thiopurines in current medical practice: Molecular mechanisms and contributions to therapy-related cancer. Nature Reviews. Cancer, 8(1), 24–36. doi:nrc2292 [pii]. https://doi.org/10.1038/nrc2292
  • Klett, J., Núñez-Salgado, A., Dos Santos, H. G., Cortés-Cabrera, Á., Perona, A., Gil-Redondo, R., Abia, D., Gago, F., & Morreale, A. (2012, September 11). MM-ISMSA: An ultrafast and accurate scoring function for protein-protein docking. Journal of Chemical Theory and Computation, 8(9), 3395–3408. https://doi.org/10.1021/ct300497z
  • Liyanage, V. R., Jarmasz, J. S., Murugeshan, N., Del Bigio, M. R., Rastegar, M., & Davie, J. R. (2014, October 22). DNA modifications: Function and applications in normal and disease states. Biology, 3(4), 670–723. https://doi.org/10.3390/biology3040670
  • Lomax, M. E., Folkes, L. K., & O’Neill, P. (2013, October). Biological consequences of radiation-induced DNA damage: Relevance to radiotherapy. Clinical Oncology (Royal College of Radiologists (Great Britain)), 25(10), 578–585. https://doi.org/10.1016/j.clon.2013.06.007
  • Maier, J. A., Martinez, C., Kasavajhala, K., Wickstrom, L., Hauser, K. E., & Simmerling, C. (2015, August 11). ff14SB: Improving the accuracy of protein side chain and backbone parameters from ff99SB. Journal of Chemical Theory and Computation, 11(8), 3696–3713. https://doi.org/10.1021/acs.jctc.5b00255
  • Maki, H., & Sekiguchi, M. (1992, January 16). MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis. Nature, 355(6357), 273–275. https://doi.org/10.1038/355273a0
  • Makurat, S., Cournia, Z., & Rak, J. (2022, January 10). Inactive-to-active transition of human thymidine kinase 1 revealed by molecular dynamics simulations. Journal of Chemical Information and Modeling, 62(1), 142–149. https://doi.org/10.1021/acs.jcim.1c01157
  • Man, P., Fábry, M., Sieglová, I., Kavan, D., Novák, P., & Hnízda, A. (2019, April). Thiopurine intolerance-causing mutations in NUDT15 induce temperature-dependent destabilization of the catalytic site. Biochimica et Biophysica Acta. Proteins and Proteomics, 1867(4), 376–381. https://doi.org/10.1016/j.bbapap.2019.01.006
  • Martínez-Rosell, G., Giorgino, T., & De Fabritiis, G. (2017, July 24). PlayMolecule ProteinPrepare: A web application for protein preparation for molecular dynamics simulations. Journal of Chemical Information and Modeling, 57(7), 1511–1516. https://doi.org/10.1021/acs.jcim.7b00190
  • McGibbon, R. T., Beauchamp, K. A., Harrigan, M. P., Klein, C., Swails, J. M., Hernández, C. X., Schwantes, C. R., Wang, L. P., Lane, T. J., & Pande, V. S. (2015, October 20). MDTraj: A modern open library for the analysis of molecular dynamics trajectories. Biophysical Journal, 109(8), 1528–1532. https://doi.org/10.1016/j.bpj.2015.08.015
  • Perona, A., Ros, M. P., Mills, A., Morreale, A., & Gago, F. (2020, October). Distinct binding of cetirizine enantiomers to human serum albumin and the human histamine receptor H(1). Journal of Computer-Aided Molecular Design, 34(10), 1045–1062. https://doi.org/10.1007/s10822-020-00328-8
  • Pettersen, E. F., Goddard, T. D., Huang, C. C., Meng, E. C., Couch, G. S., Croll, T. I., Morris, J. H., & Ferrin, T. E. (2021, January). UCSF ChimeraX: Structure visualization for researchers, educators, and developers. Protein Science : A Publication of the Protein Society, 30(1), 70–82. https://doi.org/10.1002/pro.3943
  • Pui, C.-H., Robison, L. L., & Look, A. T. (2008). Acute lymphoblastic leukaemia. Lancet (London, England), 371(9617), 1030–1043. https://doi.org/10.1016/S0140-6736(08)60457-2
  • Rehling, D., Zhang, S. M., Jemth, A.-S., Koolmeister, T., Throup, A., Wallner, O., Scaletti, E., Moriyama, T., Nishii, R., Davies, J., Desroses, M., Rudd, S. G., Scobie, M., Homan, E., Berglund, U. W., Yang, J. J., Helleday, T., & Stenmark, P. (2021). Crystal structures of NUDT15 variants enabled by a potent inhibitor reveal the structural basis for thiopurine sensitivity. The Journal of Biological Chemistry, 296, 100568. https://doi.org/10.1016/j.jbc.2021.100568
  • Singer, N. K., Sánchez-Murcia, P. A., Ernst, M., & González, L. (2022, July 25). Unravelling the turn-on fluorescence mechanism of a fluorescein-based probe in GABA(A) receptors. Angewandte Chemie (International ed. in English), 61(30), e202205198. https://doi.org/10.1002/anie.202205198
  • Singh, M., Bhatia, P., Khera, S., & Trehan, A. (2017, November). Emerging role of NUDT15 polymorphisms in 6-mercaptopurine metabolism and dose related toxicity in acute lymphoblastic leukaemia. Leukemia Research, 62, 17–22. https://doi.org/10.1016/j.leukres.2017.09.012
  • Song, Y., DiMaio, F., Wang, R. Y., Kim, D., Miles, C., Brunette, T., Thompson, J., & Baker, D. (2013, October 8). High-resolution comparative modeling with RosettaCM. Structure (London, England : 1993), 21(10), 1735–1742. https://doi.org/10.1016/j.str.2013.08.005
  • Studer, G., Rempfer, C., Waterhouse, A. M., Gumienny, R., Haas, J., & Schwede, T. (2020, April 15). QMEANDisCo-distance constraints applied on model quality estimation. Bioinformatics (Oxford, England), 36(8), 2647. https://doi.org/10.1093/bioinformatics/btaa058
  • Suiter, C. C., Moriyama, T., Matreyek, K. A., Yang, W., Scaletti, E. R., Nishii, R., Yang, W., Hoshitsuki, K., Singh, M., Trehan, A., Parish, C., Smith, C., Li, L., Bhojwani, D., Yuen, L. Y. P., Li, C.-K., Li, C.-H., Yang, Y.-L., Walker, G. J., … Yang, J. J. (2020). Massively parallel variant characterization identifies NUDT15 alleles associated with thiopurine toxicity. Proceedings of the National Academy of Sciences of the United States of America, 117(10), 5394–5401. https://doi.org/10.1073/pnas.1915680117
  • Swenberg, J. A., Lu, K., Moeller, B. C., Gao, L., Upton, P. B., Nakamura, J., & Starr, T. B. (2011). Endogenous versus exogenous DNA adducts: Their role in carcinogenesis, epidemiology, and risk assessment. Toxicological Sciences, 120(1), S130–S145. https://doi.org/10.1093/toxsci/kfq371
  • Terdiman, J. P., Gruss, C. B., Heidelbaugh, J. J., Sultan, S., & Falck-Ytter, Y. T. (2013, December). American Gastroenterological Association institute guideline on the use of thiopurines, methotrexate, and anti-TNF-α biologic drugs for the induction and maintenance of remission in inflammatory Crohn’s disease. Gastroenterology, 145(6), 1459–1463. https://doi.org/10.1053/j.gastro.2013.10.047
  • Topal, M. D., & Baker, M. S. (1982, April). DNA precursor pool: A significant target for N-Methyl-N-nitrosourea in C3H/10T1/2 clone 8 cells. Proceedings of the National Academy of Sciences of the United States of America, 79(7), 2211–2215. https://doi.org/10.1073/pnas.79.7.2211
  • Valerie, N. C. K., Hagenkort, A., Page, B. D. G., Masuyer, G., Rehling, D., Carter, M., Bevc, L., Herr, P., Homan, E., Sheppard, N. G., Stenmark, P., Jemth, A.-S., & Helleday, T. (2016, September 15). NUDT15 hydrolyzes 6-thio-deoxyGTP to mediate the anticancer efficacy of 6-thioguanine. Cancer Research, 76(18), 5501–5511. https://doi.org/10.1158/0008-5472.CAN-16-0584
  • Vanommeslaeghe, K., Hatcher, E., Acharya, C., Kundu, S., Zhong, S., Shim, J., Darian, E., Guvench, O., Lopes, P., Vorobyov, I., & Mackerell, A. D. (2010, March). CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. Journal of Computational Chemistry, 31(4), 671–690. https://doi.org/10.1002/jcc.21367
  • Virtanen, P., Gommers, R., Oliphant, T. E., Haberland, M., Reddy, T., Cournapeau, D., Burovski, E., Peterson, P., Weckesser, W., Bright, J., van der Walt, S. J., Brett, M., Wilson, J., Millman, K. J., Mayorov, N., Nelson, A. R. J., Jones, E., Kern, R., Larson, E., … van Mulbregt, P. (2020, March). SciPy 1.0: Fundamental algorithms for scientific computing in python. Nature Methods, 17(3), 261–272. https://doi.org/10.1038/s41592-019-0686-2
  • Wang, J., Wolf, R. M., Caldwell, J. W., Kollman, P. A., & Case, D. A. (2004, July 15). Development and testing of a general amber force field. Journal of Computational Chemistry, 25(9), 1157–1174. https://doi.org/10.1002/jcc.20035
  • Yang, S.-K., Hong, M., Baek, J., Choi, H., Zhao, W., Jung, Y., Haritunians, T., Ye, B. D., Kim, K.-J., Park, S. H., Park, S.-K., Yang, D.-H., Dubinsky, M., Lee, I., McGovern, D. P. B., Liu, J., & Song, K. (2014, September). A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia. Nature Genetics, 46(9), 1017–1020. https://doi.org/10.1038/ng.3060
  • Zhang, S. M., Desroses, M., Hagenkort, A., Valerie, N. C. K., Rehling, D., Carter, M., Wallner, O., Koolmeister, T., Throup, A., Jemth, A.-S., Almlöf, I., Loseva, O., Lundbäck, T., Axelsson, H., Regmi, S., Sarno, A., Krämer, A., Pudelko, L., Bräutigam, L., … Helleday, T. (2020, October). Development of a chemical probe against NUDT15. Nature Chemical Biology, 16(10), 1120–1128. https://doi.org/10.1038/s41589-020-0592-z

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