Nuevos insights sobre las propiedades fisicoquímicas del transportador de monoamina VMAT2 humano y su modo de interacción con el neurotransmisor serotonina: Un análisis in silico
DOI:
https://doi.org/10.33448/rsd-v9i7.4491Palabras clave:
Predicción fisicoquímica; Modelado molecular; Transportadores de monoaminas; Serotonina; Acoplamiento molecular.Resumen
VMAT2 son glicoproteínas capaces de transportar monoaminas desde vesículas presinápticas a hendiduras sinápticas durante la activación neuronal. Presente en muchas especies de animales, incluidos mamíferos, reptiles y aves, esta proteína se ha estudiado ampliamente, sin embargo, se sabe poco sobre sus características fisicoquímicas y el modo de interacción con ligandos nativos o no. Para caracterizar mejor el VMAT2 humano, el presente estudio se desarrolló para explorar diversos parámetros físico-químicos, bioquímicos y estructurales relacionados con este neurotransportador a través de herramientas in silico. En este trabajo, se presentan ideas nuevas y relevantes sobre la estructura y su mecanismo de interacción con 5-HT.
Citas
Asadi, S., Gholizadeh, Z., Jamali, M., Nazirzadeh, A., & Habibi, S. (2016). VMAT2 Gene molecular study of 2,000 peoples in the religious behavior and belief in God of the citizens of the city of Tabriz in Iran. International Journal of Genetic Science, 3(1), 1-6.
Barbosa, A. R., Lima, M. M. S., Marques, C. M., & Ferraz, A. C. (2012). Efeito da suplementação com ácidos graxos poliinsaturados da família ômega-3 sobre a expressão de proteínas na substância cinzenta periaquidutal de ratos wistar. Cadernos da Escola de Saúde, 8(1), 130-143.
Bezerra, L. C. C., Queiroz, E. W. A., & Freire, J. E. C. (2018). Predição físico-química, modelagem e análise do mecanismo de interação da quitinase Mo-chi1 [Moringa oleifera, LAM.], com poli-β-(1-4)-N-acetil-D-glucosamina: uma abordagem in silico. Desafios, 5(1), 111-120.
Buchan, D. W. A., & Jones, D. T. (2019). The PSIPRED Protein Analysis Workbench: 20 years on. Nucleic Acids Research, 47(W1), W402–W407.
Ceroni, A., Passerini, A., Vullo, A., & Frasconi, P. (2006). DISULFIND: A disulfide bonding state and cysteine connectivity prediction server. Nucleic acids research, 34(suppl 2), W177-W181.
Chen, V. B., Arendall, W. B. 3rd., Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., Murray, L. W., Richardson, J. S., & Richardson, D. C. (2010). MolProbity: All-atom structure validation for macromolecular crystallography. Acta Crystallographica Section D: Biological Crystallography, 66(1), 12-21.
Colovos, C.; & Yeates, T. O. (1993). Verification of protein structures: patterns of nonbonded atomic interactions. Protein science, 2(9), 1511-1519.
Dein, S. (2020). Transcendence, religion and social bonding. Archive for the Psychology of Religion, 42(1), 77-88.
Drozdetskiy, A., Cole, C., Procter, J., & Barton, G. J. (2015). JPred4: a protein secondary structure prediction server. Nucleic Acids Research, 43(W1), W389-W394.
Eiden, L. E., & Weihe, E. (2011). VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse. Annals of the New York Academy of Sciences, 1216(1), 86-98.
Eisenberg, D., Lüthy, R., & Bowie, J. U. (1997). VERIFY3D: Assessment of protein models with three-dimensional profiles. In: Methods in enzymology. Academic Press, 277, 396-404.
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. (2010). Features and development of Coot. Acta Crystallographica Section D: Biological Crystallography, 66(4), 486-501.
Eswar, N., John, B., Mirkovic, N., Fiser, A., Ilyin, V. A., Pieper, U., Stuart, A. C., Marti-Renom, M. A., Madhusudhan, M. S., Yerkovich, B., & Sali, A. (2003). Tools for comparative protein structure modeling and analysis. Nucleic acids research, 31(13), 3375-3380.
Fernandez-Fuentes, N., Madrid-Aliste, C. J., Rai, B. K., Fajardo, J. E., & Fiser, A. (2007). M4T: A comparative protein structure modeling server. Nucleic acids research, 35(suppl 2), W363-W368.
Ferrè, F., & Clote, P. (2005). DiANNA: A web server for disulfide connectivity prediction. Nucleic acids research, 33(suppl 2), W230-W232.
Finn, R D., Attwood, T. K., Babbitt, P. C., Bateman, A., Bork, P., Bridge, A. J., Chang, H-Y., Dosztányi, Z., El-Gebali, S., Fraser, M., Gough, J., Haft, D., Holliday, G. L., Huang, H., Huang, X., Letunic, I., Lopez, R., Lu, S., Marchler-Bauer, A., Mi, H., Mistry, J., Natale, D. A., Necci, M., Nuka, G., Orengo, C. A., Park, Y., Pesseat, S., Piovesan, D., Potter, S. C., Rawlings, N. D., Redaschi, N., Richardson, L., Rivoire, C., Sangrador-Vegas, A., Sigrist, C., Sillitoe, I., Smithers, B., Squizzato, S., Sutton, G., Thanki, N., Thomas, P. D., Tosatto, S. C. E., Wu, C. H., Xenarios, I., Yeh, L-S., Young, S-Y., & Mitchell, A. L. (2016). InterPro in 2017 - Beyond protein family and domain annotations. Nucleic acids research, 45(D1), D190-D199.
Frank, K., & Manfred, J. (2008). High-performance signal peptide prediction based on sequence alignment techniques. Bioinformatics, 24(19), 2172-2176.
Gainetdinov, R. R., Fumagalli, F., Wang, Y. M., Jones, S. R., Levey, A. I., Miller, G. W., & Caron, M. G. (1998). Increased MPTP neurotoxicity in vesicular monoamine transporter 2 heterozygote knockout mice. Journal of Neurochemistry, 70(5), 1973-1978.
Gasteiger, E., Hoogland, C., Gattiker, A., Duvaud, S., Wilkins, M. R.;, Appel, R. D., & Bairoch, A. (2005). Protein identification and analysis tools on the ExPASy server. In: The proteomics protocols handbook. Humana press, 571-607.
Goldberg, T., Hecht, M., Hamp, T., Karl, T., Yachdav, G., Ahmed, N., Altermann, U., Angerer, P., Ansorge, S., Balasz, K., Bernhofer, M., Betz, A., Cizmadija, L., Do, K. T., Gerke1, J., Greil, R., Joerdens, V., Hastreiter, M., Hembach, K., Herzog, M., Kalemanov, M., Kluge, M., Meier, A., Nasir, H., Neumaier, U., Prade, V., Reeb, J., Sorokoumov, A., Troshani, I., Vorberg, S., Waldraff, S., Zierer, J., Nielsen, H., & Rost, B. (2014). LocTree3 prediction of localization. Nucleic acids research, 42(W1), W350-W355.
Goodsell, D. S., Zardecki, C., Di Costanzo, L., Duarte, J. M., Hudson, B. P., Persikova, I., Segura, J., Shao, C., Voigt, M., Westbrook, J. D., Young, J. Y., & Burley, S. K. (2020). RCSB Protein Data Bank: Enabling biomedical research and drug discovery. Protein Science, 29(1), 52-65.
Grazhdankin, E., Stepniewski, M., & Xhaard, H. (2020) Modeling membrane proteins: the importance of cysteine amino-acids. Journal of Structural Biology, 209(1), 107400.
Harris, N. J., Findlay, H. E., Sanders, M. R., Kedzierski, M., Santos, Á., & Booth, P. J. (2017). Comparative stability of major facilitator superfamily transport proteins. European Biophysics Journal, 46(7), 655-663.
Huang, M., He, W., Rajagopal, L., Kudwa, A., Grigoriadis, D. E., & Meltzer, H. Y. (2020). Effects of NBI-98782, a selective vesicular monoamine transporter 2 (VMAT2) inhibitor, on neurotransmitter efflux and phencyclidine-induced locomotor activity: Relevance to tardive dyskinesia and antipsychotic action. Pharmacology Biochemistry and Behavior, 190, 172872.
Imani, M., Hosseinkhani, S., Ahmadian, A., & Nazari, M. (2010). Design and introduction of a disulfide bridge in firefly luciferase: increase of thermostability and decrease of pH sensitivity. Photochemical & Photobiological Sciences, 9(8), 1167-1177.
Jassen, A. K., Brown, J. M., Panas, H. N., Miller, G. M., Xiao, D., & Madras, B. K. (2005). Variants of the primate vesicular monoamine transporter-2. Molecular Brain Research, 139(2), 251-257.
Jiang, D., Kong, Y., Ren, S., Cai, H., Zhang, Z., Huang, Z., Peng, F., Hua, F., Guan, Y., & Xie, F. (2020). Decreased striatal vesicular monoamine transporter 2 (VMAT2) expression in a type 1 diabetic rat model: A longitudinal study using micro-PET/CT. Nuclear Medicine and Biology, 82(83), 89-95.
Kelley, L. A., Mezulis, S., Yates, C. M., Wass, M. N., & Sternberg, M. J. E. (2015). The Phyre2 web portal for protein modeling, prediction and analysis. Nature protocols, 10(6), 845-858.
Kim, S., Chen, J., Cheng, T., Gindulyte, A.; He, J., He, S., Li, Q., Shoemaker, B. A., Thiessen, P. A., Yu, B., Zaslavsky, L., Zhang, J., & Bolton, E. (2018). PubChem 2019 update: Improved access to chemical data. Nucleic acids research, 47(D1), D1102-D1109.
Ko, J., Park, H., Heo, L., & Seok, C. (2012). GalaxyWEB server for protein structure prediction and refinement. Nucleic acids research, 40(W1), W294-W297.
Lee, J., Sands, Z. A., & Biggin, P. C. (2016). A Numbering System for MFS Transporter Proteins. Frontiers in Molecular Biosciences, 3(21), 1-13.
Lyskov, S., Chou, F-C., Conchúir, S. Ó., Der, B. S., Drew, K., Kuroda, D., Xu, J., Weitzner, B. D., Renfrew, P. D., Sripakdeevong, P., Borgo, B., Havranek, J. J., Kuhlman, B., Kortemme, T., Bonneau, R., Gray, J. J., & Das, R. (2013). Serverification of molecular modeling applications: the Rosetta Online Server that Includes Everyone (ROSIE). PloS one, 8(5), e63906.
Marchler-Bauer, A., Derbyshire, M. K., Gonzales, N. R., Lu, S., Chitsaz, F., Geer, L. Y., Geer, R. C., He, J., Gwadz, M., Hurwitz, D. I., Lanczycki, C. J., Lu, F., Marchler, G. H., Song, J. S., Thanki, N., Wang, Z., Yamashita, R. A., Zhang, D., Zheng, C., & Bryant, S. H. (2015). CDD: NCBI's conserved domain database. Nucleic acids research, 43(D1), D222-D226.
Miller, G. W., Erickson, J. D., Perez, J. T., Penland, S. N., Mash, D. C., Rye, D. B., & Levey, A. I. (1999). Immunochemical analysis of vesicular monoamine transporter (VMAT2) protein in Parkinson’s disease. Experimental Neurology, 156(1), 138-148.
Monteiro-Júnior, J. E., Sousa, S. C. O, Silva, M. N., Medeiros, S. C., Freire, C. M. A. S., & Freire, J. E. C. (2017). New biochemical and physicochemical insights on a muskmelon [Cucumis melo (L.)] chitinase. IOSR Journal Of Pharmacy. 7(1), 46-57.
MULVIHILL, K. G. (2019). Presynaptic regulation of dopamine release: Role of the DAT and VMAT2 transporters. Neurochemistry International, 122, 94-105.
Nagano, R., & Masuda, K. (2014). Establishment of a signal peptide with cross-species compatibility for functional antibody expression in both Escherichia coli and chinese hamster ovary cells. Biochemical and biophysical research communications, 447(4), 655-659.
Narendran, R., Lopresti, B. J., Martinez, D., Mason, N. S., Himes, M., May, M. A., Daley, D. C., Price, J. C., Mathis, C. A., & Frankle, W. G. (2012). In vivo evidence for reduced striatal vesicular monoamine transporter (VMAT2) availability in cocaine abusers. The American Journal of Psychiatry, 169(1), 55-63.
Nickell, J. R., Siripurapu, K. B., Vartak, A., Crooks, P. A., & Dwoskin, L. P. (2014). The Vesicular Monoamine Transporter-2: An important pharmacological target for the discovery of novel therapeutics to treat methamphetamine abuse. Advances in Pharmacology, 69, 71-106.
Nyarko, J. N. K., Quartey, M. O., Heistad1, R M., Pennington, P. R., Poon, L. J., Knudsen, K. J., Allonby, O., Zawily, A. M. E., Freywald, A., Rauw, G., Baker, G. B., & Mousseau, D. D. (2018). Glycosylation states of pre- and post-synaptic markers of 5-HT neurons differ with sex and 5-HTTLPR genotype in cortical autopsy samples. Frontiers in Neuroscience, 12(545), 1-17.
O’Brien, C., Liang, G., Farber, R., & Kurlan, R. (2016). Selective VMAT Inhibitors for Tourette Syndrome. Austin Journal of Neurological Disorders & Epilepsy, 3(2), 1019.
Owens, D. C. (2019). Tardive dyskinesia update: treatment and management. BJPsych Advances, 25, 78-89.
Pecic, S., Milosavic, N., Rayat, G., Maffei, A., & Harris, P. E. (2019). A novel optical tracer for VMAT2 applied to live cell measurements of vesicle maturation in cultured human β-cells. Scientific Reports, 9(1), 1-13.
Robinson, P. J., Kanemura, S., Cao, X., & Bulleid, N. J. (2020). Protein secondary structure determines the temporal relationship between folding and disulfide formation. Journal of Biological Chemistry, 295(8), 2438-2448.
Rykunov, D., Steinberger, E., Madrid-Aliste, C. J., & Fiser, A. (2009). Improved scoring function for comparative modeling using the M4T method. Journal of structural and functional genomics, 10(1), 95-99.
Savosina, P., Karasev, D., Veselovsky, A., Miroshnichenko, Y., & Sobolev, B. (2020). Functional and structural features of proteins associated with alternative splicing. International Journal of Biological Macromolecules, 147, 513-520.
Sreeram, V., Shagufta, S., & Kagadkar, F. (2019). Role of vesicular monoamine transporter 2 inhibitors in tardive dyskinesia management. Cureus, 11(8), e5471.
Torres, B., & Ruoho, A. E. (2014). N-terminus regulation of VMAT2 mediates methamphetamine-stimulated efflux. Neuroscience, 259,194-202.
Wang, Y. M., Gainetdinov, R. R., Fumagalli, F., Xu, F., Jones, S. R., Bock, C. B., Miller, G. W., Wightman, R. M., & Caron, M. G. (1997). Knockout of the vesicular monoamine transporter 2 gene results in neonatal death and supersensitivity to cocaine and amphetamine. Neuron, 19(6), 1285-1296.
Wang, S. C., Davejan, P., Hendargo, K. J., Javadi-Razaz, I., Chou, A., Yee, D. C., Ghazi, F., Lam, K. J. K., Conn, A. M., Madrigal, A., Medrano-Soto, A., & Saier Jr., M. H. (2020). Expansion of the Major Facilitator Superfamily (MFS) to include novel transporters as well as transmembrane-acting enzymes. Biochimica et Biophysica Acta – Biomembranes, 20, 183277.
Waterhouse, A., Bertoni, M., Bienert, S., Studer, G., Tauriello, G., Gumienny, R., Heer, F. T., De Beer, T. A. P., Rempfer, C., Bordoli, L., Lepore, R., & Schwede, T. (2018). SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic acids research, v. 46(W1), W296-W303.
Wiederstein, M., & Sippl, M. J. (2007). ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic acids research, 35(suppl-2), W407-W410.
Wiradharma, N., Khoe, U., Hauser, C. A., Seow, S. V., Zhang, S., & Yang, Y. Y. (2011). Synthetic cationic amphiphilic α-helical peptides as antimicrobial agents. Biomaterials, 32(8), 2204-2212.
Wu, S., & Zhang, Y. (2007). LOMETS: A local meta-threading-server for protein structure prediction. Nucleic acids research, 35(10), 3375-3382.
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