Análisis computacional de la captación de fosfato en Staphylococcus aureus y prospección de posibles inhibidores
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https://doi.org/10.24933/e-usf.v9i1.466Palabras clave:
Unión cósmica, Bioinformática, Resistencia bacterianaResumen
Staphylococcus aureus es un patógeno oportunista asociado con varias infecciones y una creciente resistencia a los antibióticos. El fosfato es esencial para los procesos celulares y, en S. aureus, su captación se produce a través de transportadores de tipo ABC, en los que la proteína SBP juega un papel fundamental. Este estudio tuvo como objetivo identificar y caracterizar la proteína SBP de
S. aureus a través de enfoques bioinformáticos, buscando la identificación de posibles ligandos capaces de interferir en su función. Se utilizaron bases de datos, plataformas en línea y herramientas bioinformáticas para la caracterización estructural y modelado de la proteína y sus ligandos. El análisis reveló un transportador completo, siendo la proteína PstS responsable de la unión y captación de fosfato. Su estructura, típica de las proteínas SBP tipo II, presenta dos residuos claves en la interacción con el fosfato: D116 y T171. El acoplamiento molecular indicó que las moléculas de sulfato, nitrato y varias de fosfato tienen afinidad por PstS, con valores de energía libre negativos. Los resultados sugieren que los compuestos que contienen fosfato pueden interactuar con PstS, interfiriendo potencialmente con el transporte de fosfato. Estos hallazgos abren el camino para el desarrollo de moléculas que comprometen la captación de fosfato por S. aureus, reduciendo su viabilidad y potencial infeccioso.
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AGUENA, M. Análise transcricional do operon pst de Escherichia coli. Tese (Doutorado em Microbiologia) —Instituto de Ciências Biomédicas da Universidade de São Paulo. São Paulo, p. 25. 2007. DOI: https://doi.org/10.11606/T.42.2007.tde-30012008-094907
ARMENTEROS, José Juan Almagro et al. SignalP 5.0 improves signal peptide predictions using deep neural networks. Naturebiotechnology, v. 37, n. 4, p.420-423, 2019. DOI: https://doi.org/10.1038/s41587-019-0036-z
ARYA, N.; KAUR, DR. A. Molecular Docking: A Review Paper. International Journal of Innovative Research in Engineering & Management, p. 140–146, 1 fev. 2022. DOI: https://doi.org/10.55524/ijirem.2022.9.1.25
BARAK, Y.; VAN RIJN, J. Relationship between Nitrite Reduction and Active Phosphate Uptake in the Phosphate-Accumulating Denitrifier Pseudomonas sp. Strain JR 12. Applied and Environmental Microbiology, v. 66, n. 12, p. 5236–5240, dez. 2000. DOI: https://doi.org/10.1128/aem.66.12.5236-5240.2000
CASSAT, J. E.; SKAAR, E. P. Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity. Seminars in Immunopathology, v. 34, n. 2, p. 215–235, 3 nov. 2011. DOI: https://doi.org/10.1007/s00281-011-0294-4
CHEUNG, G. Y. C.; BAE, J. S.; OTTO, M. Pathogenicity and virulence of Staphylococcus a u r e u s. Virulence, v. 1 2, n. 1, p. 5 4 7 – 5 6 9, 3 1 j a n. 2 0 2 1. D O I: https://doi.org/10.1080/21505594.2021.1878688
CHUDOBOVA, D. et al. Comparison of the effects of silver phosphate and selenium nanoparticles on Staphylococcus aureus growth reveals potential for selenium particles to prevent infection. FEMS Microbiology Letters, v. 351, n. 2, p. 195–201, 30 dez. 2013. DOI: https://doi.org/10.1111/1574-6968.12353
DEMONTE, A. M.; DIEZ A. D. M.; NALEWAY C.; IGLESIAS A. A.; BALLICORA M. A. Monofluorophosphate Blocks Internal Polysaccharide Synthesis in Streptococcus mutans. PLOS ONE, v. 12, n. 1, p. e0170483, 26 jan. 2017. DOI: https://doi.org/10.1371/journal.pone.0170483
FERRARIS, D. M.; SPALLEK R.; OEHLMANN W.; SIGH M.; RIZZI M. Crystal structure of the Mycobacterium tuberculosis phosphate binding protein PstS3. Proteins: Structure, Function, and Bioinformatics, v. 82, n. 9, p. 2268–2274, 24 mar. 2014. DOI: https://doi.org/10.1002/prot.24548
GAO, M.; SKOLNICK, J. A Comprehensive Survey of Small-Molecule Binding Pockets in Proteins. PLoS Computational Biology, v. 9, n. 10, p. e1003302, 24 out. 2013. DOI: https://doi.org/10.1371/journal.pcbi.1003302
GAUDREAULT, F.; CHARTIER, M.; NAJMANOVICH, R. Side-chain rotamer changes upon ligand binding: common, crucial, correlate with entropy and rearrange hydrogen bonding. Bioinformatics, v. 28, n. 18, p. i423–i430, 7 set. 2012. DOI: https://doi.org/10.1093/bioinformatics/bts395
GILMOUR, R. B. Phosphoric Acids and Phosphates. Kirk-Othmer Encyclopedia of Chemical Technology, p. 1–51, 12 jun. 2019. DOI: https://doi.org/10.1002/0471238961.1608151907011804.a01.pub3
GONZALEZ, D.; RICHEZ M.; BERGONZI C.; CHABRIERE E.; ELIAS M. Crystal structure of the phosphate-binding protein (PBP-1) of an ABC type phosphate transporter from Clostridium perfringens. Scientific Reports, v. 4, n. 1, 16 out. 2014. DOI: https://doi.org/10.1038/srep06636
GUEDES, I. A. et al. New machine learning and physics-based scoring functions for drug discovery. Scientific Reports, v. 11, n. 1, 4 fev. 2021. DOI: https://doi.org/10.1038/s41598-021-82410-1
HALLGREN, Jeppe et al. DeepTMHMM predicts alpha and beta transmembrane proteins using deep neural networks. BioRxiv, 2022. DOI: https://doi.org/10.1101/2022.04.08.487609
HOLLENSTEIN, K.; DAWSON, R. J.; LOCHER, K. P. Structure and mechanism of ABC transporter proteins. Current Opinion in Structural Biology, v. 17, n. 4, p. 412–418, ago. 2007. DOI: https://doi.org/10.1016/j.sbi.2007.07.003
HORSMAN, G. P.; ZECHEL, D. L. Phosphonate Biochemistry. Chemical Reviews, v. 117, n. 8, p. 5704–5783, 27 out. 2016. DOI: https://doi.org/10.1021/acs.chemrev.6b00536
KELLIHER, J. L. et al. Staphylococcus aureus Preferentially Liberates Inorganic Phosphate from Organophosphates in Environments where This Nutrient Is Limiting. Journal of Bacteriology, v. 202, n. 22, 31 ago. 2020. DOI: https://doi.org/10.1128/jb.00264-20
KROGH, A.; LARSSON, B.; VON HEIJNE, G.; SONNHAMMER, E.L.L. Predicting transmembrane protein topology with a hidden Markov model: Application to complete genomes. Journalof Molecular Biology, v. 305, n.3, p. :567-580, 2001. DOI: https://doi.org/10.1006/jmbi.2000.4315
LABOTKA, R. J.; A OMACHI. Erythrocyte anion transport of phosphate analogs. Journal of biological chemistry/The Journal of biological chemistry, v. 262, n. 1, p. 305–311, 1 jan. 1987. DOI: https://doi.org/10.1016/S0021-9258(19)75927-4.
LARKIN M.A., BLACKSHIELDS G., BROWN N.P., CHENNA R., MCGETTIGAN P.A., MCWILLIAM H., VALENTIN F., WALLACE I.M., WILM A., LOPEZ R., THOMPSON J.D., GIBSON T.J. AND HIGGINS D.G. Clustal W and Clustal X version 2.0. bioinformatics, v. 23, n. 21, p. 2947-2948, 2007. DOI: https://doi.org/10.1093/bioinformatics/btm404
LETUNIC, Ivica; KHEDKAR, Supriya; BORK, Peer. SMART: recent updates, new developments and status in 2020. Nucleic acids research, v. 49, n. D1, p. D458-D460, 2021. https://doi.org/10.1093/nar/gkaa937
LEWIS, VG.; WEEN, MP.; MCDEVITT, CA. The role of ATP-binding cassette transporters in bacterial pathogenicity. Protoplasma, v. 249, p. 919-942, 2012. DOI: https://doi.org/10.1007/s00709-011-0360-8
LEWINSON, O.; LIVNAT-LEVANON, N. Mechanism of Action of ABC Importers: Conservation, Divergence, and Physiological Adaptations. Journal of Molecular Biology, v. 429, n. 5, p. 606–619, mar. 2017. DOI: https://doi.org/10.1016/j.jmb.2017.01.010
LIMA, M. A.; RUDD T. R.; FERNING D. G.; YATES E. A. Phosphorylation and sulfation share a common biosynthetic pathway, but extend biochemical and evolutionary diversity of biological macromolecules in distinct ways. Journal of The Royal Society Interface, v. 19, n. 193, ago. 2022. DOI: https://doi.org/10.1098/rsif.2022.0391
LOCHER, K. P. Mechanistic diversity in ATP-binding cassette (ABC) transporters. Nature Structural & Molecular Biology, v. 23, n. 6, p. 487–493, jun. 2016. DOI: 10.1038/ nsmb.3216 DOI: https://doi.org/10.1038/nsmb.3216
LOGHMAN-ADHAM, M. Use of phosphonocarboxylic acids as inhibitors of sodium phosphate cotransport. General Pharmacology: The Vascular System, v. 27, n. 2, p. 305– 312, mar. 1996. DOI: https://doi.org/10.1016/0306-3623(95)02017-9
MIRDITA, M.; SCHÜTZE K.; MORIWAKI Y.; HEO L.; OVCHINNIKOV S.; STEINEGGER M. ColabFold: making protein folding accessible to all. Nature Methods, v. 19, p. 1–4, 30 maio 2022. DOI: https://doi.org/10.1038/s41592-022-01488-1
MLYNARCZYK-BONIKOWSKA, B. KOWALEWSKI C.; KROLAK-ULINSKA A.; MARUSZA W. Molecular Mechanisms of Drug Resistance in Staphylococcus aureus. International Journal of Molecular Sciences, v. 23, n. 15, p. 8088, 1 jan. 2022. DOI: https://doi.org/10.3390/ijms23158088
MOLLICA, L.; BESSA L. M.; HANOULLE X.; JENSEN M. R.; BLACKLEDGE M.; SCHNEIDER R. Binding Mechanisms of Intrinsically Disordered Proteins: Theory, Simulation, and Experiment. Frontiers in Molecular Biosciences, v. 3, 9 set. 2016. DOI: https://doi.org/10.3389/fmolb.2016.00052
NISHI, H.; SHAYTAN, A.; PANCHENKO, A. R. Physicochemical mechanisms of protein regulation by phosphorylation. Frontiers in Genetics, v. 5, 7 ago. 2014. DOI: https://doi.org/10.3389/fgene.2014.00270
O'BOYLE, Noel M.; BANCK M.; JAMES C. A.; MORLEY C.; VANDERMEERSCH T.; HUTCHISON G. R. Open Babel: An open chemical toolbox. Journal of cheminformatics, v. 3, p. 1-14, 2011. DOI: https://doi.org/10.1186/1758-2946-3-33
PAHONȚU, E. et al. Synthesis, Characterization, Crystal Structure and Antimicrobial Activity of Copper (II) Complexes with the Schiff Base Derived from 2-Hydroxy-4-Methoxybenzaldehyde. Molecules, v. 20, n. 4, p. 5771–5792, 2 abr. 2015.DOI: https://doi.org/10.3390/molecules20045771
PEGOS, V. R. Nascimento J. F.; SOBREIRA T. J. P.; PAULETTI B. A.; PAES-LEME A. Phosphate regulated proteins of Xanthomonas citri subsp. citri: a proteomic approach. Journal of proteomics, v. 108, p. 78-88, 2014. DOI: https://doi.org/10.1016/j.jprot.2014.05.005
PEREIRA, CT.; ROESLER, C.; FARIA, JN.; FESSEL, MR.; BALAN, A. Sulfate-Binding Protein (Sbp) from Xanthomonas citri: Structure and Functional Insights. Molecular Plant Microbe Interactions, v.30, p. 578-588, 2017. DOI: https://doi.org/10.1094/mpmi-02-17-0032-r
POPOVA, Y. THAYUMANAVAN, P. LONATI, E. AGROCHAO,M. THEVELEN, J.M. Transport and signaling through the phosphate-binding site of the yeast Pho84 phosphate transceptor. Proceedings of the National Academy of Sciences, v. 107, n. 7, p. 2890–2895, 1 fev. 2010. DOI: https://doi.org/10.1073/pnas.0906546107
PRILUSKKY, J. FOLDER, CE. ZEEV-BEN-MORDEHAI, T. RYDBERG, EH. MAN, O. BECKMANN, JS. SILMAN, I. SUSSMAN, JL. FoldIndex©: a simple tool to predict whether a given protein sequence is intrinsically unfolded. Bioinformatics, v. 21, n. 16, p. 3435-3438, 2005. DOI: https://doi.org/10.1093/bioinformatics/bti537
REECE, J. B., URRY, L. A., CAIN, M. L., WASSERMAN, S. A., MINORSKY, P. V. JACKSON, R. B. (2011). Membrane structure and function. In Campbell biology, 10th ed., p. 127. San Francisco, CA: Pearson.
REES, DC. JOHNSON, E. LEWINSON, O. ABC transporters: the power to change. Nature Reviews Molecular Cell Biology, v.10, p. 218-227, 2009. DOI: https://doi.org/10.1038/nrm2646
SALAMOV, A.; SOLOVYEVAND, V. Automatic annotation of microbial genomes and metagenomic sequences. In: LI, R.W. (ed.). Metagenomics and its applications in agriculture, biomedicine and environmental studies. New York: Nova Science Publishers, 2011. p. 61-78.
SAMPAIO, A.; PEGOS, VANESSA; OSHIRO, ELISA; BALAN, A. The periplasmic binding protein NrtT affects xantham gum production and pathogenesis in Xanthomona citri. FEBS Open Bio, v. 7, p. 1499-1514, 2017. DOI: https://doi.org/10.1002/2211-5463.12281
SANDOVAL, J.; SCOTTIE, E. Investigating the role of phosphate homeostasis in Staphylococcus aureus virulence. 2021. Tese (Mestrado em Microbiologia) - Universidade de Illinois Urbana-Champaign, Illinois
SANTOS, K. B. et al. Highly Flexible Ligand Docking: Benchmarking of the DockThor Program on the LEADS-PEP Protein–Peptide Data Set. Journal of Chemical Information and Modeling, v. 60, n. 2, p. 667–683, 10 jan. 2020. DOI: https://pubs.acs.org/doi/10.1021/acs.jcim.9b00905
SCHEEPERS, G. H.; LYCKLAMA A NIJEHOLT, J. A.; POOLMAN, B. An updated structural classification of substrate-binding proteins. FEBS Letters, v. 590, n. 23, p. 4393–4401, 23 out. 2016. DOI: https://doi.org/10.1002/1873-3468.12445
SEVRAIN, M. C.; BERCHEL, M.; COUTHON, H.; JAFFRÈS, Phosphonic acid: preparation and applications. Beilstein Journal of Organic Chemistry, v. 13, p. 2186–2213, 20 out. 2017. DOI: https://doi.org/10.3762/bjoc.13.219
SHIGI, Y. Inhibition of bacterial isoprenoid synthesis by fosmidomycin, a phosphonic acid-containing antibiotic. Journal of Antimicrobial Chemotherapy, v. 24, n. 2, p. 131–145, 1989. DOI: https://doi.org/10.1093/jac/24.2.131
SHINITZKY, M.; HAYMOVITZ R.; NEMAS M.; CAHANA N.; MAMILLAPALLI R.; SEGER R. Induction of intracellular signalling by cyclic glycerophosphates and their deoxy analogues. European Journal of Biochemistry, v. 267, n. 9, p. 2547–2554, 25 dez. 2001. DOI: https://doi.org/10.1046/j.1432-1327.2000.01265.x
SILVA, K.; PRAZERES R. A.; CURSELLI F.; CREMONESI A. S. Structural Characterization and Molecular Docking of Polyamine Transporters in Enterobacter Cloacae. SciMed Central, 16 maio 2023 DOI: https://doi.org/10.47739/2333-7109/1039
TANAKA, KJ.; SONG, S.; MASON, K.; PINKETT, HW. Selective substrate uptake: The role of ATP-binding cassette (ABC) importers in pathogenesis. Biochimica et Biophysica Acta (BBA) - Biomembranes, v. 1860, p.868-877, 2017. DOI: https://doi.org/10.1016/j.bbamem.2017.08.011
TER BEEK, Josy; GUSKOV, Albert; SLOTBOOM, Dirk Jan. Structural diversity of ABC transporters. Journal of General Physiology, v. 143, n. 4, p. 419-435, 2014. https://doi.org/ 10.1002/1873-3468.13935
TER-OVANESSIAN, L. M. P.; RIGAUD B.; MEZZETTI A.; LAMBERT J.; MAUREL M. Carbamoyl phosphate and its substitutes for the uracil synthesis in origins of life scenarios. Scientific Reports, v. 11, n. 1, 29 set. 2021. DOI: https://doi.org/10.1038/s41598-021-98747-6
TJADEN, B. A computational system for identifying operons based on RNA-seq data. Methods, v. 176, abr. 2019. DOI: https://doi.org/10.1016/j.ymeth.2019.03.026
UNNI, Samir et al. Web servers and services for electrostatics calculations with APBS and PDB2PQR. Journal of computational chemistry, v. 32, n. 7, p. 1488-1491, 2011. https:// doi.org/10.1002/jcc.21720
VON HEIJNE, G. The signal peptide. Journal of Membrane Biology, v. 115, p. 195-201, 1990. DOI: https://doi.org/10.1007/BF01868635
WALLQVIST A.; COVELL D. G. Docking enzyme-inhibitor complexes using a preference based free-energy surface. Proteins: Structure, Function, and Bioinformatics, v. 25, n. 4, p. 403–419, ago. 1996. DOI: https://doi.org/10.1002/(SICI)1097-0134(199608)25:4<403::AID-PROT1>3.0.CO;2-E
ZHANG, Y. et al. Discovery and structure of a widespread bacterial ABC transporter specific for ergothioneine. Nature Communications, v. 13, n. 1, 8 dez. 2022. DOI: https://doi.org/10.1038/s41467-022-35277-3
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