Поиск производных ингибиторов протеинфосфатаз, потенциально связанных с регуляцией цитоскелета растений

Поиск производных ингибиторов протеинфосфатаз, потенциально связанных с регуляцией цитоскелета растений

Aims. Okadaic acid (OA) strongly inhibits protein serine/threonine phosphatases PP1 and PP2A/2B. In comparison with the other inhibitors the inhibitory effect of OA is strongest for PP2A, followed by PP1, and then PP2B. This toxin is now used as powerful research tool of an increasingly wide variety...

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Veröffentlicht in:Фактори експериментальної еволюції організмів
Datum:2015
Hauptverfasser: Самофалова, Д.А., Карпов, П.А., Блюм, Я.Б.
Format: Artikel
Sprache:Russian
Veröffentlicht: Інститут молекулярної біології і генетики НАН України 2015
Schlagworte:
Молекулярна генетика та геноміка рослин
Online Zugang:https://nasplib.isofts.kiev.ua/handle/123456789/177460
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Назва журналу:Digital Library of Periodicals of National Academy of Sciences of Ukraine
Zitieren:Поиск производных ингибиторов протеинфосфатаз, потенциально связанных с регуляцией цитоскелета растений / Д.А. Самофалова, П.А. Карпов, Я.Б. Блюм // Фактори експериментальної еволюції організмів: Зб. наук. пр. — 2015. — Т. 17. — С. 87-91. — Бібліогр.: 20 назв. — рос.

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Digital Library of Periodicals of National Academy of Sciences of Ukraine
id nasplib_isofts_kiev_ua-123456789-177460
record_format dspace
spelling Самофалова, Д.А.
Карпов, П.А.
Блюм, Я.Б.
2021-02-15T18:35:12Z
2021-02-15T18:35:12Z
2015
Поиск производных ингибиторов протеинфосфатаз, потенциально связанных с регуляцией цитоскелета растений / Д.А. Самофалова, П.А. Карпов, Я.Б. Блюм // Фактори експериментальної еволюції організмів: Зб. наук. пр. — 2015. — Т. 17. — С. 87-91. — Бібліогр.: 20 назв. — рос.
2219-3782
https://nasplib.isofts.kiev.ua/handle/123456789/177460
577.151: 57.05:57.052.6
Aims. Okadaic acid (OA) strongly inhibits protein serine/threonine phosphatases PP1 and PP2A/2B. In comparison with the other inhibitors the inhibitory effect of OA is strongest for PP2A, followed by PP1, and then PP2B. This toxin is now used as powerful research tool of an increasingly wide variety of cellular events regulated by reversible protein phosphorylation. Because of the lack of highly PP1 and PP2A/2B selective inhibitors, design and search of new biologically active OA derivatives is extremely important. Methods. Modeling of PP1 and PP2A spatial structures were performed using SWISS-MODEL server. The ligands for molecular docking were prepared using CCDC Hermes molecular editor. Flexible docking of OA derivatives was performed using CCDC GOLD Suite 5.1. Binding site for PP1 was specified in 15 Е radius about -NE2 (HIS125), PP2А in 20 Е radius about -ND2 (ASN117), and for РР4 in 15 Е radius about - ND1 (ARG129). For docking evaluations, CCDC GOLD scoring functions (ChemScore, GoldScore and ASP) were used. Finally, docking results were evaluated by molecular dynamics simulations in GROMACS. Results. Using template based modeling and human structures of PP1 (PDB: 1U32) and PP2A (PDB: 2IE4) in complex with okadaic acid 3D-models of plant homologues from Arabidopsis thaliana, Emericella nidulans and Salmonella typhimurium were build. A high level of sequence and structure identity in plant and animal phosphatases allow us to conclude similarity of OA binding sites in PP1, PP2A and PP4. Based on chemoinformatic analysis using PubChem (http://pubchem.ncbi.nlm.nih. gov) and ZINK (http://zinc.docking.org/) databases, 26 OA-derivatives of were selected. Complexes with selected ligand were predicted by results of flexible docking and evaluated by docking scoring functions and MD results. Conclusions. As a result, five compounds not previously described as PP1, PP2A and PP4 inhibitors, were selected.
Частично исследование было выполнено в рамках проекта УНТЦ#5215: «Поиск эффективных ингибиторов протеинфосфатаз с помощью нанохимических подходов и оценка их биологической эффективности in silico».
ru
Інститут молекулярної біології і генетики НАН України
Фактори експериментальної еволюції організмів
Молекулярна генетика та геноміка рослин
Поиск производных ингибиторов протеинфосфатаз, потенциально связанных с регуляцией цитоскелета растений
Search for new protein phosphatase inhibitors – potential regulators of the plant cytoskeleton
Article
published earlier
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
collection DSpace DC
title Поиск производных ингибиторов протеинфосфатаз, потенциально связанных с регуляцией цитоскелета растений
spellingShingle Поиск производных ингибиторов протеинфосфатаз, потенциально связанных с регуляцией цитоскелета растений
Самофалова, Д.А.
Карпов, П.А.
Блюм, Я.Б.
Молекулярна генетика та геноміка рослин
title_short Поиск производных ингибиторов протеинфосфатаз, потенциально связанных с регуляцией цитоскелета растений
title_full Поиск производных ингибиторов протеинфосфатаз, потенциально связанных с регуляцией цитоскелета растений
title_fullStr Поиск производных ингибиторов протеинфосфатаз, потенциально связанных с регуляцией цитоскелета растений
title_full_unstemmed Поиск производных ингибиторов протеинфосфатаз, потенциально связанных с регуляцией цитоскелета растений
title_sort поиск производных ингибиторов протеинфосфатаз, потенциально связанных с регуляцией цитоскелета растений
author Самофалова, Д.А.
Карпов, П.А.
Блюм, Я.Б.
author_facet Самофалова, Д.А.
Карпов, П.А.
Блюм, Я.Б.
topic Молекулярна генетика та геноміка рослин
topic_facet Молекулярна генетика та геноміка рослин
publishDate 2015
language Russian
container_title Фактори експериментальної еволюції організмів
publisher Інститут молекулярної біології і генетики НАН України
format Article
title_alt Search for new protein phosphatase inhibitors – potential regulators of the plant cytoskeleton
description Aims. Okadaic acid (OA) strongly inhibits protein serine/threonine phosphatases PP1 and PP2A/2B. In comparison with the other inhibitors the inhibitory effect of OA is strongest for PP2A, followed by PP1, and then PP2B. This toxin is now used as powerful research tool of an increasingly wide variety of cellular events regulated by reversible protein phosphorylation. Because of the lack of highly PP1 and PP2A/2B selective inhibitors, design and search of new biologically active OA derivatives is extremely important. Methods. Modeling of PP1 and PP2A spatial structures were performed using SWISS-MODEL server. The ligands for molecular docking were prepared using CCDC Hermes molecular editor. Flexible docking of OA derivatives was performed using CCDC GOLD Suite 5.1. Binding site for PP1 was specified in 15 Е radius about -NE2 (HIS125), PP2А in 20 Е radius about -ND2 (ASN117), and for РР4 in 15 Е radius about - ND1 (ARG129). For docking evaluations, CCDC GOLD scoring functions (ChemScore, GoldScore and ASP) were used. Finally, docking results were evaluated by molecular dynamics simulations in GROMACS. Results. Using template based modeling and human structures of PP1 (PDB: 1U32) and PP2A (PDB: 2IE4) in complex with okadaic acid 3D-models of plant homologues from Arabidopsis thaliana, Emericella nidulans and Salmonella typhimurium were build. A high level of sequence and structure identity in plant and animal phosphatases allow us to conclude similarity of OA binding sites in PP1, PP2A and PP4. Based on chemoinformatic analysis using PubChem (http://pubchem.ncbi.nlm.nih. gov) and ZINK (http://zinc.docking.org/) databases, 26 OA-derivatives of were selected. Complexes with selected ligand were predicted by results of flexible docking and evaluated by docking scoring functions and MD results. Conclusions. As a result, five compounds not previously described as PP1, PP2A and PP4 inhibitors, were selected.
issn 2219-3782
url https://nasplib.isofts.kiev.ua/handle/123456789/177460
citation_txt Поиск производных ингибиторов протеинфосфатаз, потенциально связанных с регуляцией цитоскелета растений / Д.А. Самофалова, П.А. Карпов, Я.Б. Блюм // Фактори експериментальної еволюції організмів: Зб. наук. пр. — 2015. — Т. 17. — С. 87-91. — Бібліогр.: 20 назв. — рос.
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first_indexed 2025-12-07T16:41:46Z
last_indexed 2025-12-07T16:41:46Z
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