بررسی قدرت اتصال آنزیم های DEP-A و DEP-B با مایکوتوکسین 15ADON با استفاده از داکینگ مولکولی

نوع مقاله : مقاله کامل

نویسندگان

1 دانشگاه فردوسی مشهد

2 علوم دامی دانشکده کشاورزی دانشگاه فردوسی مشهد

3 پژوهشکده گیاهان و مواد اولیه دارویی دانشگاه شهید بهشتی

4 Ferdowsi University of Mashhad

چکیده

دی‌اکسی‌نیوالنول (DON) رایج‌ترین مایکوتوکسین آلوده‌کننده‌ی غلات است که با روش‌های رایج نظیر جاذب‌ها قابل کنترل نیست. از این رو، روش‌های مبتنی بر آنزیم‌ها جهت سم‌زدایی این نوع مایکوتوکسین ها پیشنهاد می‌شود. هدف از مطالعه‌ی حاضر بررسی برهمکنش آنزیم‌های DEP-A و DEP-B با کموتایپ‌های مایکوتوکسین DON نظیر 15- استیل-دی‌اکسی‌نیوالنول (15ADON) از طریق داکینگ مولکولی می‌باشد. ساختار سه بعدی پروتئین های DEP-A و DEP-B با استفاده از سرور SWISS MODEL پیش‌بینی شد. سپس، پایداری این ساختارها در شرایط دینامیکی مولکولی مورد ارزیابی قرار گرفتند. بدین منظور شبیه‌سازی با کمک نرم‌افزار GROMACS انجام شد و سپس منحنی RMSDمربوط به این دو آنزیم جهت بررسی پایداری ساختار رسم شد. به‌منظور بررسی برهم‌کنش های آنزیم DEP-A با 15ADON و DEP-B با حدواسط ایجاد شده از مرحله‌ی قبل یعنیOxid 15ADON از سرور آنلاین H-DOCK استفاده شد. بررسی ساختارهای پیش‌بینی‌شده توسط پلات‌های ERRAT، Verify3D، Z-score و Ramachandran نشان داد که پیش‌بینی ساختارها با موفقیت انجام شده‌است. منحنی های RMSD نشان داد که DEP-A و DEP-B به ترتیب در 240 و 40 نانوثانیه با میزان 58/0 و 35/0 nm پایدار شده‌اند. نتایج مربوط به داکینگ مولکولی نیز نشان داد که هر دو آنزیم DEP-A و DEP-B به ترتیب با انرژی اتصال نسبتا قوی (90/157- و 78/141-) به سوبسترا متصل شده‌اند. در نهایت می‌توان نتیجه گرفت که هر دو آنزیم مورد مطالعه قادر به اتصال به کموتایپ 15ADON در جایگاه مناسب بوده که نشان می‌دهد این آنزیم‌ها می‌توانند در غیر فعال سازی این کموتایپ موثر واقع شوند. اگرچه مطالعات آزمایشگاهی به منظور تایید این نتایج مورد نیاز می‌باشد.

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

Investigating of the binding energy of DEP-A and DEP-B enzymes with DON mycotoxin chemotype by molecular docking

نویسندگان [English]

  • Zahra Mousavi 1
  • Mohammad hadi Sekhavati 2
  • Mohsen Farzaneh 3
  • Ali Javadmanesh 4
1 Ferdowsi University of Mashhad
2 Animal science, agriculture, ferdowsi university of mashhad
3 Medicinal Plants and Drugs Research Institute, Shahid Beheshti University
4 Ferdowsi University of Mashhad
چکیده [English]

15acetyl-deoxynivalenol (15ADON) is the most common chemotype of dioxynivalenol (DON) mycotoxin, which cannot be controlled by common methods such as absorbents. Hence, enzyme-based methods are suggested for detoxification of these types of mycotoxins, which requires bioinformatics studies before laboratory investigations. Therefore, the aim of the present study was to investigate the binding energy of DEP-A and DEP-B enzymes with 15ADON through molecular docking. The three-dimensional structures of DEP-A and DEP-B proteins were predicted using the SWISS MODEL server. Then, the stability of these structures was evaluated in molecular dynamic conditions. For this purpose, the simulation was carried out with GROMACS software and then the RMSD curve of these two enzymes was drawn to check the stability of the predicted structure. H-DOCK online server was used to performed the interaction of DEP-A enzyme with 15ADON and DEP-B with Oxid15ADON intermediate. Checking the accuracy of the predicted structures by ERRAT Verify3D, Z-score and Ramachandran plots showed that the prediction of tertiary structures successfully performed. The RMSD curves showed that DEP-A and DEP-B were stabilized in 240 and 40 nanoseconds with 0.58 and 0.35 nm, respectively. The results of molecular docking also showed that both DEP-A and DEP-B enzymes could bind to their substrates with relatively strong binding energy -157.90 and -141.78, respectively. Overall, it can be concluded that both studied enzymes were able to bind to the 15ADON chemotype of DON in the appropriate position, which shows that these enzymes can be effective in deactivating this chemotype, although laboratory studies are needed to confirm the results

کلیدواژه‌ها [English]

  • Molecular Docking
  • Mycotoxin
  • Enzyme
  • 15-Acetyl-Deoxynivalenol

مراجع

  1. Abraham, N., Schroeter, K. L., Zhu, Y., Chan, J., Evans, N., Kimber, M. S., ... & Seah, S. Y. (2022). Structure-Function characterization of an aldo-keto reductase involved in detoxification of the mycotoxin, deoxynivalenol.
  2. Alizadeh, A., Braber, S., Akbari, P., Kraneveld, A., Garssen, J., & Fink-Gremmels, J. (2016). Deoxynivalenol and its modified forms: are there major differences?. Toxins, 8(11), 334.
  3. Beg, M., Thakur, S. C., & Meena, L. S. (2018). Structural prediction and mutational analysis of Rv3906c gene of Mycobacterium tuberculosis H37Rv to determine its essentiality in survival. Advances in Bioinformatics, 2018.
  4. Carere, J., Hassan, Y. I., Lepp, D., & Zhou, T. (2017). The enzymatic detoxification of the mycotoxin deoxynivalenol: identification of DEP-A from the DON epimerization pathway. Microbial Biotechnology, 11(6), 1106-1111.
  5. Carere, J., Hassan, Y.I., Lepp, D. and Zhou, T., 2018. The identification of DepB: an enzyme responsible for the final detoxification step in the deoxynivalenol epimerization pathway in Devosia mutans 17-2-E-8. Frontiers in Microbiology, 9, p.1573.
  6. Chlebicz, A., & Śliżewska, K. (2020). In vitro detoxification of aflatoxin B1, deoxynivalenol, fumonisins, T-2 toxin and zearalenone by probiotic bacteria from genus Lactobacillus and Saccharomyces cerevisiae yeast. Probiotics and antimicrobial proteins, 12(1), 289-301.
  7. Creppy, E. E. (2002). Update of survey, regulation and toxic effects of mycotoxins in Europe. Toxicology letters, 127(1-3), 19-28.
  8. Fang, Q. A., Du, M., Chen, J., Liu, T., Zheng, Y., Liao, Z., ... & Wang, J. (2020). Degradation and detoxification of aflatoxin B1 by tea-derived Aspergillus niger RAF106. Toxins, 12(12), 777.
  9. Farhana, A., & Lappin, S. L. (2022). Biochemistry, lactate dehydrogenase. In StatPearls [Internet]. StatPearls Publishing.
  10. He, J. W., Bondy, G. S., Zhou, T., Caldwell, D., Boland, G. J., & Scott, P. M. (2015). Toxicology of 3-epi-deoxynivalenol, a deoxynivalenol-transformation product by Devosia mutans 17-2-E-8. Food and Chemical Toxicology, 84, 250-259.
  11. He, W. J., Shi, M. M., Yang, P., Huang, T., Zhao, Y., Wu, A. B., ... & Liao, Y. C. (2020). A quinone-dependent dehydrogenase and two NADPH-dependent aldo/keto reductases detoxify deoxynivalenol in wheat via epimerization in a Devosia strain. Food chemistry, 321, 126703.
  12. Ikunaga, Y., Sato, I., Grond, S., Numaziri, N., Yoshida, S., Yamaya, H., ... & Ito, M. (2011). Nocardioides sp. strain WSN05-2, isolated from a wheat field, degrades deoxynivalenol, producing the novel intermediate 3-epi-deoxynivalenol. Applied microbiology and biotechnology, 89(2), 419-427.
  13. Javadmanesh, A., Mohammadi, E., Mousavi, Z., Azghandi, M., & Tanhaiean, A. (2021). Antibacterial effects assessment on some livestock pathogens, thermal stability and proposing a probable reason for different levels of activity of thanatin. Scientific reports, 11(1), 1-10.
  14. Kratzer, R., Kavanagh, K. L., Wilson, D. K., & Nidetzky, B. (2004). Studies of the enzymic mechanism of Candida tenuis xylose reductase (AKR 2B5): X-ray structure and catalytic reaction profile for the H113A mutant. Biochemistry, 43(17), 4944-4954.
  15. Liu, M., Zhao, L., Gong, G., Zhang, L., Shi, L., Dai, J., ... & Sun, L. (2022). Invited review: Remediation strategies for mycotoxin control in feed. Journal of Animal Science and Biotechnology, 13(1), 1-16.
  16. Mousavi, S. Z., Kazemi, S. A., Mahroughi, M., & Tanhaeian, A. (2021). Evaluation of antibacterial activity and toxicity of enterocin P peptide and two essential oils against animal pathogens. Veterinary Researches & Biological Products, 34(3), 48-54. doi: 10.22092/vj.2020.342383.1707.
  17. Mousavi, S.Z. and Javadmanesh, A., 2022, February. Molecular docking of Enterocin-P peptide with DNA: an in silico study. In The 1st International and the 10th National Iranian Conference on Bioinformatics.
  18. Mousavi, Z., Rashidian, Z., Zeraatpisheh, Y., & Javadmanesh, A. (2022). Molecular docking of bacteriocin enterocin P peptide with mastitis-causing E. coli antigen in cattle. Veterinary Researches and Biological Products. 137: 115-123.
  19. Nemaysh, V., & Luthra, P. M. (2017). Computational analysis revealing that K634 and T681 mutations modulate the 3D-structure of PDGFR-β and lead to sunitinib resistance. RSC advances, 7(60), 37612-37626.
  20. Qiu, T., Wang, H., Yang, Y., Yu, J., Ji, J., Sun, J., ... & Sun, X. (2021). Exploration of biodegradation mechanism by AFB1-degrading strain Aspergillus niger FS10 and its metabolic feedback. Food Control, 121, 107609.
  21. Roshanak, S., Yarabbi, H., Shahidi, F., Tabatabaei Yazdi, F., Movaffagh, J. and Javadmanesh, A., 2023. Effects of adding poly-histidine tag on stability, antimicrobial activity and safety of recombinant buforin I expressed in periplasmic space of Escherichia coli. Scientific Reports, 13(1), p.5508.
  22. Rozeboom, H. J., Yu, S., Mikkelsen, R., Nikolaev, I., Mulder, H. J., & Dijkstra, B. W. (2015). Crystal structure of quinone‐dependent alcohol dehydrogenase from P seudogluconobacter saccharoketogenes. A versatile dehydrogenase oxidizing alcohols and carbohydrates. Protein Science, 24(12), 2044-2054.
  23. Sherif, S. O., Salama, E. E., & Abdel-Wahhab, M. A. (2009). Mycotoxins and child health: The need for health risk assessment. International journal of hygiene and environmental health, 212(4), 347-368.
  24. Vidal, L. S., Kelly, C. L., Mordaka, P. M., & Heap, J. T. (2018). Review of NAD (P) H-dependent oxidoreductases: Properties, engineering and application. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics, 1866(2), 327-347.
  25. Yan, P., Liu, Z., Liu, S., Yao, L., Liu, Y., Wu, Y., & Gong, Z. (2020). Natural occurrence of deoxynivalenol and its acetylated derivatives in Chinese maize and wheat collected in 2017. Toxins, 12(3), 200.
  26. Yang, H., Yan, R., Li, Y., Lu, Z., Bie, X., Zhao, H., ... & Chen, M. (2022). Structure–Function Analysis of a Quinone-Dependent Dehydrogenase Capable of Deoxynivalenol Detoxification. Journal of Agricultural and Food Chemistry.

 

تحقیقات دامپزشکی و فرآورده‌های بیولوژیک
دوره 37، شماره 1
فروردین 1403
صفحه 15-26

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سابقه مقاله

  • تاریخ دریافت: 29 فروردین 1402
  • تاریخ بازنگری: 04 تیر 1402
  • تاریخ پذیرش: 06 تیر 1402

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