Реконструкція просторової структури комплексів рослинних протеїнфосфатаз типу 1, 2а, 4 з мікроцистином-LR

  • Д. А. Самофалова Державна установа «Інститут харчової біотехнології та геноміки НАН України»,Україна, 04123, м. Київ, вул. Осиповського, 2A
  • П. А. Карпов Державна установа «Інститут харчової біотехнології та геноміки НАН України»,Україна, 04123, м. Київ, вул. Осиповського, 2A
  • О. В. Раєвський Державна установа «Інститут харчової біотехнології та геноміки НАН України»,Україна, 04123, м. Київ, вул. Осиповського, 2A
  • Я. Б. Блюм Державна установа «Інститут харчової біотехнології та геноміки НАН України»,Україна, 04123, м. Київ, вул. Осиповського, 2A
DOI: https://doi.org/10.7124/FEEO.v20.791

Анотація

Aim. The major toxicity of Microcystin-LR (MCLR) has been ascribed to its potent ability to inhibit serine/threonine-specific protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A). Although MCLR is widely used in animal models its selectivity for these enzymes of plant origin is not still investigated in details for phylogenetically diversified sources. Methods. The spatial structure of plant PP1, PP2A, PP4 protein phosphatases was reconstructed with homology modeling method. Flexible docking of MCLR was performed using CCDC GOLD Suite 5.3. For docking evaluations, GOLD scoring functions were used. Results. Information about amino acids, involved in ligand binding, was obtained from 8 experimentally proved human MCLR-PP1 and PP2A complexes. The sites of microcystin-LR binding with plant protein phosphatases (type-1, 2А and 4) were proved by comparative analysis and molecular docking. A high level of sequence and structure identity of plant and animal phosphatases allow us to conclude similarity of MCLR binding in PP1, PP2A and PP4.

Keywords: microcystin-LR, protein phosphatase, specific interaction, molecular docking.

Посилання

Codd G.A., Azevedo S.M.F.O., Bagchi S.N., Burch M.D., Carmichael W.W., Harding W.R., Kaya K., Utkilen H.C. International hydrological programme CYANONET: A global network for cyanobacterial bloom and toxin risk management initial situation assessment and recommendations. UNESCO, Paris: IHP-VI: Technical Documents in Hydrology, No. 76, 2005. 138 р.

Honkanen R.E., Zwiller J., Moore R.E., Daily S.L., Khatra B.S., Dukelow M., Boynton A.L. Characterization of microcystin-LR, a potent inhibitor of type 1 and type 2A protein phosphatases. J. Biol. Chem. 1990. V. 265(32). Р. 19401-19404.

MacKintosh C., Beattie K.A., Klumpp S., Cohen P., Codd G.A. Cyanobacterial microcystin-LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants. FEBS Lett. 1990. V. 264(2). Р. 187-192. doi: 10.1016/0014-5793(90)80245-E

Bettina C. Hitzfeld, Stefan J. Höger and Daniel R. Dietrich. Cyanobacterial toxins: removal during drinking water treatment, and human risk assessment. Environm. Health Perspectives. 2000. V. 108. Р. 113-122. doi: 10.1289/ehp.00108s1113

Sassolas A., Catanante G., Fournier D., Marty J.L. Development of a colorimetric inhibition assay for microcystin-LR detection: comparison of the sensitivity of different protein phosphatases. Talanta. 2011. V. 85(5). P. 2498-2503. doi: 10.1016/j.talanta.2011.07.101

Dawson J.F., Holmes C.F. Molecular mechanisms underlying inhibition of protein phosphatases by marine toxins. Front. Biosci. 1999. V. 4. P. 646-658. doi: 10.2741/A461

Vale C., Botana L. Marine toxins and the cytoskeleton: okadaic acid and dinophysistoxins. FEBS J. 2008. V. 275. P. 6060-6066. doi: 10.1111/j.1742-4658.2008.06711.x

Máthé C., Beyer D., M-Hamvas M., Vasas G. The effects of microcystins (cyanobacterial heptapeptides) on the eukaryotic cytoskeletal system. Mini Rev. Med. Chem. 2016. V. 16(13). P. 1063-1077. doi: 10.2174/1389557516666160219130732

Samofalova D., Karpov P., Blium Ya. Poshuk roslynnykh molekuliarnykh misheney selektyvnykh inhibitoriv seryn-treonin spetsyfichnykh proteinfosfataz. Visnyk L'vivs'koho un-tu. Seriia biol. 2014. V. 68. P. 392-404. [in Ukrainian]

Samofalova D.A., Karpov P.A., Blium Ya.B. Osoblyvosti lihand-bilkovoi vzaiemodii inhibitoriv proteinfosfataz, potentsiyno pov'iazanykh z tsytoskeletom. Faktory eksperymental'noi evoliutsii orhanizmiv. 2016. V. 19. P. 229-233. [in Ukrainian]

Cole J.C., Nissink J.W.M., Taylor R. Protein-ligand docking and virtual screening with GOLD. In: Virtual Screening in Drug Discovery (J. Alvarez and B. Shoichet, Eds.), CRC Press, Boca Raton, Fla, USA, 2005. P. 379-415. doi: 10.1201/9781420028775.ch15

De Wulf P., Montani F., Visintin R. Protein phosphatases take the mitotic stage. Curr. Op. Cell Biol. 2009. V. 21. P. 806-815. doi: 10.1016/j.ceb.2009.08.003

Kumar R., Musiyenko A., Oldenburg A., Adams B., Barik S. Post-translational generation of constitutively active cores from larger phosphatases in the malaria parasite, Plasmodium falciparum: implications for proteomics. BMC Mol. Biol. 2004. V. 5(6). doi: 10.1186/1471-2199-5-6.