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Volume 11, Issue 4 (Vol.11 No.4 Jan 2023)
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Galindo-Hernández O, García-Salazar L A, García-González V G, Díaz-Molina R, Vique-Sánchez J L. Potential Inhibitors of The OTUB1 Catalytic Site to Develop an Anti-Cancer Drug Using In-Silico Approaches. rbmb.net 2023; 11 (4) :684-693
URL: http://rbmb.net/article-1-969-en.html
URL: http://rbmb.net/article-1-969-en.html
Octavio Galindo-Hernández 
, Lizbeth Angelina García-Salazar , Victor Guadalupe García-González , Raúl Díaz-Molina , José Luis Vique-Sánchez *
, Lizbeth Angelina García-Salazar , Victor Guadalupe García-González , Raúl Díaz-Molina , José Luis Vique-Sánchez *
Autonomous University of Baja California, School of Medicine Campus Mexicali, Mexicali, BC, México.
Abstract: (1827 Views)
Background: Cancer continues worldwide. It has been reported that OTUB1, a cysteine protease, plays a critical role in a variety of tumors and is strongly related to tumor proliferation, migration, and clinical prognosis by its functions on deubiquitination. Drug advances continue against new therapeutic targets. In this study we used OTUB1 to develop a specific pharmacological treatment to regulate deubiquitination by OTUB1. The aim of this research is to regulate OTUB1 functions.
Methods: By molecular docking in a specific potential OTUB1 interaction site between Asp88, Cys91, and His26 amino acids, using a chemical library of over 500,000 compounds, we selected potential inhibitors of the OTUB1 catalytic site.
Results: Ten compounds (OT1 - OT10) were selected by molecular docking to develop a new anti-cancer drug to decrease OTUB1 functions in cancer processes.
Conclusions: OT1 – OT10 compounds could be interacting in the potential site between Asp88, Cys91, and His265 amino acids in OTUB1. This site is necessary for the deubiquitinating function of OTUB1. Therefore, this study shows another way to attack cancer.
Methods: By molecular docking in a specific potential OTUB1 interaction site between Asp88, Cys91, and His26 amino acids, using a chemical library of over 500,000 compounds, we selected potential inhibitors of the OTUB1 catalytic site.
Results: Ten compounds (OT1 - OT10) were selected by molecular docking to develop a new anti-cancer drug to decrease OTUB1 functions in cancer processes.
Conclusions: OT1 – OT10 compounds could be interacting in the potential site between Asp88, Cys91, and His265 amino acids in OTUB1. This site is necessary for the deubiquitinating function of OTUB1. Therefore, this study shows another way to attack cancer.
Type of Article: Original Article |
Subject:
Molecular Biology
Received: 2022/06/9 | Accepted: 2022/06/24 | Published: 2023/04/3
Received: 2022/06/9 | Accepted: 2022/06/24 | Published: 2023/04/3
References
1. Balakirev MY, Tcherniuk SO, Jaquinod M, Chroboczek J. Otubains: a new family of cysteine proteases in the ubiquitin pathway. EMBO Rep. 2003;4(5):517-22. [DOI:10.1038/sj.embor.embor824] [PMID] [PMCID]
2. Wiener R, DiBello AT, Lombardi PM, Guzzo CM, Zhang X, Matunis MJ, et al. E2 ubiquitin-conjugating enzymes regulate the deubiquitinating activity of OTUB1. Nat Struct Mol Biol. 2013;20(9):1033-9. [DOI:10.1038/nsmb.2655] [PMID] [PMCID]
3. Saldana M, VanderVorst K, Berg AL, Lee H, Carraway KL. Otubain 1: a non-canonical deubiquitinase with an emerging role in cancer. Endocr Relat Cancer. 2019;26(1):R1-14. [DOI:10.1530/ERC-18-0264] [PMID] [PMCID]
4. Wu Q, Huang Y, Gu L, Chang Z, Li G-M. OTUB1 stabilizes mismatch repair protein MSH2 by blocking ubiquitination. J Biol Chem. 2021;296:100466. [DOI:10.1016/j.jbc.2021.100466] [PMID] [PMCID]
5. Wiener R, Zhang X, Wang T, Wolberger C. The mechanism of OTUB1-mediated inhibition of ubiquitination. Nature. 2012;22;483(7391):618-22. [DOI:10.1038/nature10911] [PMID] [PMCID]
6. Pasupala N, Morrow ME, Que LT, Malynn BA, Ma A, Wolberger C. OTUB1 non-catalytically stabilizes the E2 ubiquitin-conjugating enzyme UBE2E1 by preventing its autoubiquitination. J Biol Chem. 2018;293(47):18285-95. [DOI:10.1074/jbc.RA118.004677] [PMID] [PMCID]
7. Jahan AS, Biquand E, Muñoz-Moreno R, Le Quang A, Mok CK-P, Wong HH, et al. OTUB1 Is a Key Regulator of RIG-I-Dependent Immune Signaling and Is Targeted for Proteasomal Degradation by Influenza A NS1. Cell Rep. 2020;30(5):1570-1584.e6. [DOI:10.1016/j.celrep.2020.01.015] [PMID]
8. Mulas F, Wang X, Song S, Nishanth G, Yi W, Brunn A, et al. The deubiquitinase OTUB1 augments NF-κB-dependent immune responses in dendritic cells in infection and inflammation by stabilizing UBC13. Cell Mol Immunol. 2021;18(6):1512-27. [DOI:10.1038/s41423-020-0362-6] [PMID] [PMCID]
9. Sun X-X, Dai M-S. Deubiquitinating enzyme regulation of the p53 pathway: A lesson from Otub1. World J Biol Chem. 2014;5(2):75-84.
10. Baghal-Sadriforoush S, Bagheri M, Abdi Rad I, Sotoodeh Nejadnematalahi F. PI3K Inhibition Sensitize the Cisplatin-resistant Human Ovarian Cancer Cell OVCAR3 by Induction of Oxidative Stress. Rep Biochem Mol Biol. 2022;10(4):675-85. [DOI:10.52547/rbmb.10.4.675] [PMID] [PMCID]
11. Sun X-X, Challagundla KB, Dai M-S. Positive regulation of p53 stability and activity by the deubiquitinating enzyme Otubain 1. EMBO J. 2012;31(3):576-92. [DOI:10.1038/emboj.2011.434] [PMID] [PMCID]
12. Xu Y, Xu M, Tong J, Tang X, Chen J, Chen X, et al. Targeting the Otub1/c-Maf axis for the treatment of multiple myeloma. Blood. 2021;137(11):1478-90. [DOI:10.1182/blood.2020005199] [PMID]
13. Rezai M, Saravani R, Sargazi S, Moudi M, Jafari Shahroudi M, Saravani R. Achillea Wilhelmsii C. KochHydroalcoholic Extract Induces Apoptosis and Alters LIN28B and p53 Gene Expression in Hela Cervical Cancer Cells. Reports Biochem Mol Biol. 2019;8(3):318-25.
14. Lee B-S, Kang SU, Huang M, Kim YS, Lee Y-S, Park J-Y, et al. OTUB1 knockdown promotes apoptosis in melanoma cells by upregulating TRAIL expression. BMB Rep. 2021;54(12):608-13. [DOI:10.5483/BMBRep.2021.54.12.033] [PMID] [PMCID]
15. Liao Y, Wu N, Wang K, Wang M, Wang Y, Gao J, et al. OTUB1 Promotes Progression and Proliferation of Prostate Cancer via Deubiquitinating and Stabling Cyclin E1. Front Cell Dev Biol. 2021;8. [DOI:10.3389/fcell.2020.617758] [PMID] [PMCID]
16. Liu T, Jiang L, Tavana O, Gu W. The Deubiquitylase OTUB1 Mediates Ferroptosis via Stabilization of SLC7A11. Cancer Res. 2019;79(8):1913-24. [DOI:10.1158/0008-5472.CAN-18-3037] [PMID] [PMCID]
17. Scholz CC, Rodriguez J, Pickel C, Burr S, Fabrizio J-A, Nolan KA, et al. FIH Regulates Cellular Metabolism through Hydroxylation of the Deubiquitinase OTUB1. PLoS Biol. 2016(1):e1002347. [DOI:10.1371/journal.pbio.1002347] [PMID] [PMCID]
18. Salami J, Crews CM. Waste disposal-An attractive strategy for cancer therapy. Science (80-). 2017;355(6330):1163-7. [DOI:10.1126/science.aam7340] [PMID]
19. Doherty LM, Mills CE, Boswell SA, Liu X, Hoyt CT, Gyori BM, et al. Integrating multi-omics data reveals function and therapeutic potential of deubiquitinating enzymes. bioRxiv. 2021. [DOI:10.1101/2021.08.06.455458]
20. Sivakumar D, Stein M. Binding of SARS-CoV Covalent Non-Covalent Inhibitors to the SARS-CoV-2 Papain-Like Protease and Ovarian Tumor Domain Deubiquitinases. Biomolecules. 2021;11(6):802. [DOI:10.3390/biom11060802] [PMID] [PMCID]
21. Benítez-Cardoza CG, Vique-Sánchez JL. Potential inhibitors of the interaction between ACE2 and SARS-CoV-2 (RBD), to develop a drug. Life Sci. 2020;256:117970. [DOI:10.1016/j.lfs.2020.117970] [PMID] [PMCID]
22. Halgren TA. Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94. J Comput Chem. 1996;17(5-6):490-519.
https://doi.org/10.1002/(SICI)1096-987X(199604)17:5/6<490::AID-JCC1>3.0.CO;2-P [DOI:10.1002/(SICI)1096-987X(199604)17:5/63.0.CO;2-P]
23. Vique-Sánchez JL. Potential inhibitors interacting in Neuropilin-1 to develop an adjuvant drug against COVID-19, by molecular docking. Bioorg Med Chem. 202;33:116040. [DOI:10.1016/j.bmc.2021.116040] [PMID] [PMCID]
24. ChemBridge Corp.. EXPRESS-Pick Stock. 2021.
25. Soga S, Shirai H, Kobori M, Hirayama N. Use of Amino Acid Composition to Predict Ligand-Binding Sites. J Chem Inf Model. 2007;47(2):400-6. [DOI:10.1021/ci6002202] [PMID]
26. Protein-Ligand Interaction Profiler. https://plip-tool.biotec.tu-dresden.de/plip-web/plip/index.
27. Salentin S, Schreiber S, Haupt VJ, Adasme MF, Schroeder M. PLIP: fully automated protein-ligand interaction profiler. Nucleic Acids Res. 2015;43(W1):W443-7. [DOI:10.1093/nar/gkv315] [PMID] [PMCID]
28. Labute P. The generalized Born/volume integral implicit solvent model: estimation of the free energy of hydration using London dispersion instead of atomic surface area. J Comput Chem. 2008;29(10):1693-8. 9 [DOI:10.1002/jcc.20933] [PMID]
29. Wadood A, Ghufran M, Hassan SF, Khan H, Azam SS, Rashid U. In silico identification of promiscuous scaffolds as potential inhibitors of 1-deoxy- d -xylulose 5-phosphate reductoisomerase for treatment of Falciparum malaria. Pharm Biol. 2017;55(1):19-32. [DOI:10.1080/13880209.2016.1225778] [PMID] [PMCID]
30. www.acdlabs.com/. Available from: https://www.acdlabs.com/products/percepta/index.php.
31. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7(1):42717. [DOI:10.1038/srep42717] [PMID] [PMCID]
32. PreADMET.https://preadmet.webservice.bmdrc.org/.
33. Banerjee P, Eckert AO, Schrey AK, Preissner R. ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. 2018;46(W1):W257-63. [DOI:10.1093/nar/gky318] [PMID] [PMCID]
34. Sun T, Xu Y, Xu Z, Cao B, Zhang Z, Wang Q, et al. Inhibition of the Otub1/c-Maf axis by the herbal acevaltrate induces myeloma cell apoptosis. Cell Commun Signal. 2021;19(1):24. A [DOI:10.1186/s12964-020-00676-w] [PMID] [PMCID]
35. Xu Y, Sun T, Zeng K, Xu M, Chen J, Xu X, et al. Anti-bacterial and anti-viral nanchangmycin displays anti-myeloma activity by targeting Otub1 and c-Maf. Cell Death Dis. 2020;11(9):818. [DOI:10.1038/s41419-020-03017-4] [PMID] [PMCID]
36. Juang Y-C, Landry M-C, Sanches M, Vittal V, Leung CCY, Ceccarelli DF, et al. OTUB1 Co-opts Lys48-Linked Ubiquitin Recognition to Suppress E2 Enzyme Function. Mol Cell. 2012;45(3):384-97. [DOI:10.1016/j.molcel.2012.01.011] [PMID] [PMCID]
37. Ernst A, Avvakumov G, Tong J, Fan Y, Zhao Y, Alberts P, et al. A Strategy for Modulation of Enzymes in the Ubiquitin System. Science (80- ). 2013;339(6119):590-5. [DOI:10.1126/science.1230161] [PMID] [PMCID]
38. Meuzelaar H, Vreede J, Woutersen S. Influence of Glu/Arg, Asp/Arg, and Glu/Lys Salt Bridges on α -Helical Stability and Folding Kinetics. Biophys J. 2016;110(11):2328-41. [DOI:10.1016/j.bpj.2016.04.015] [PMID] [PMCID]
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