Identification of Novel Inhibitors of a Plant Group A Protein Phosphatase Type 2C Using a Combined In Silico and Biochemical Approach
Type 2C protein phosphatases (PP2Cs) of group A play a significant role in the regulation of various processes in plants including growth, development, ion transport, and stress acclimation. In this study, we selected potential PP2C group A inhibitors using a structure-based virtual screening method...
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| Published in | Frontiers in plant science Vol. 11; p. 526460 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
Frontiers Media S.A
16.09.2020
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| Abstract | Type 2C protein phosphatases (PP2Cs) of group A play a significant role in the regulation of various processes in plants including growth, development, ion transport, and stress acclimation. In this study, we selected potential PP2C group A inhibitors using a structure-based virtual screening method followed by biochemical and
in vitro
validation. Over twenty million chemical compounds from the ZINC database were used for docking studies. The precision of the calculations was increased by an induced-fit docking protocol and the molecular mechanics/generalized Born surface area (MM/GBSA) method, which yielded approximate values for the binding energy of the protein-ligand complex. After clustering and ranking their activity, the top-ranking compounds were tested against PP2C group A members
in vitro
and their
in vivo
activity was also explored. Phosphatase activity assays identified two compounds with significant inhibitory activity against ABI1 protein ranging from around 57 to 91% at a concentration of 100 μM. Importantly, this
in vitro
activity correlated well with
in vivo
inhibition of seed germination, as expected for PP2C inhibitors. The results should promote the design of novel inhibitors with improved potency against ABI1-like and other PP2Cs that might be used in agriculture for the protection of crops against stress. |
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| AbstractList | Type 2C protein phosphatases (PP2Cs) of group A play a significant role in the regulation of various processes in plants including growth, development, ion transport, and stress acclimation. In this study, we selected potential PP2C group A inhibitors using a structure-based virtual screening method followed by biochemical and
in vitro
validation. Over twenty million chemical compounds from the ZINC database were used for docking studies. The precision of the calculations was increased by an induced-fit docking protocol and the molecular mechanics/generalized Born surface area (MM/GBSA) method, which yielded approximate values for the binding energy of the protein-ligand complex. After clustering and ranking their activity, the top-ranking compounds were tested against PP2C group A members
in vitro
and their
in vivo
activity was also explored. Phosphatase activity assays identified two compounds with significant inhibitory activity against ABI1 protein ranging from around 57 to 91% at a concentration of 100 μM. Importantly, this
in vitro
activity correlated well with
in vivo
inhibition of seed germination, as expected for PP2C inhibitors. The results should promote the design of novel inhibitors with improved potency against ABI1-like and other PP2Cs that might be used in agriculture for the protection of crops against stress. Type 2C protein phosphatases (PP2Cs) of group A play a significant role in the regulation of various processes in plants including growth, development, ion transport, and stress acclimation. In this study, we selected potential PP2C group A inhibitors using a structure-based virtual screening method followed by biochemical and in vitro validation. Over twenty million chemical compounds from the ZINC database were used for docking studies. The precision of the calculations was increased by an induced-fit docking protocol and the molecular mechanics/generalized Born surface area (MM/GBSA) method, which yielded approximate values for the binding energy of the protein-ligand complex. After clustering and ranking their activity, the top-ranking compounds were tested against PP2C group A members in vitro and their in vivo activity was also explored. Phosphatase activity assays identified two compounds with significant inhibitory activity against ABI1 protein ranging from around 57 to 91% at a concentration of 100 μM. Importantly, this in vitro activity correlated well with in vivo inhibition of seed germination, as expected for PP2C inhibitors. The results should promote the design of novel inhibitors with improved potency against ABI1-like and other PP2Cs that might be used in agriculture for the protection of crops against stress. |
| Author | Janicki, Maciej Marczak, Małgorzata Cieśla, Agata Ludwików, Agnieszka |
| AuthorAffiliation | Laboratory of Biotechnology, Faculty of Biology, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University in Poznan , Poznan , Poland |
| AuthorAffiliation_xml | – name: Laboratory of Biotechnology, Faculty of Biology, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University in Poznan , Poznan , Poland |
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| Cites_doi | 10.1038/srep37060 10.1007/s12551-016-0247-1 10.1002/pro.3235 10.1126/science.aaw8848 10.1271/bbb.90735 10.1038/srep14076 10.3390/cells9040978 10.1093/emboj/cdf316 10.1038/nature08583 10.1038/nature14123 10.1016/j.cub.2011.04.045 10.1007/s00425-009-1001-8 10.1074/jbc.M509820200 10.1021/acs.jcim.5b00559 10.1104/pp.19.00117 10.1016/j.tplants.2004.03.007 10.1016/j.tplants.2020.07.001 10.1146/annurev.arplant.54.031902.134743 10.1016/j.tplants.2015.04.001 10.1038/nsmb.1887 10.1126/science.1181829 10.1093/pcp/pcv146 10.1074/jbc.M501467200 10.1111/j.1742-4658.2012.08670.x 10.1073/pnas.1305919110 10.1093/pcp/pcq156 10.1146/annurev-arplant-042809-112122 10.1104/pp.15.01378 10.1021/ci3001277 10.1038/nsmb.1730 10.1105/tpc.107.056705 10.1016/j.cell.2016.08.029 10.1104/pp.112.202408 10.1104/pp.106.081018 10.1126/science.1215106 10.1016/j.tplants.2012.11.002 10.1038/nature08613 10.1111/j.1365-313X.2009.04054.x 10.1104/pp.16.01862 10.1093/mp/ssu025 10.1385/1-59745-267-X:23 10.1038/s41467-017-01239-3 10.1021/ci049714+ 10.1038/srep08560 10.1021/jm051033y 10.1021/acschembio.7b00650 |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Jorge Lozano-Juste, Polytechnic University of Valencia, Spain; Erwin Grill, Technical University of Munich, Germany; Aditya S. Vaidya, University of California, Riverside, United States Edited by: Goetz Hensel, Heinrich Heine University Düsseldorf, Germany This article was submitted to Plant Biotechnology, a section of the journal Frontiers in Plant Science |
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| References | Miyakawa (B23) 2013; 18 Okamoto (B27) 2013; 110 Bhaskara (B2) 2012; 160 Lozano-Juste (B15) 2020; 25 Goddard (B9) 2018; 27 Nishimura (B26) 2010; 61 Melcher (B20) 2009; 462 Vaidya (B42) 2019; 366 Swingle (B38) 2007; 365 Friso (B6) 2015; 169 Himmelbach (B11) 2002; 21 Umezawa (B40) 2010; 51 Rogers (B32) 2006; 49 Schweighofer (B35) 2004; 9 Aburai (B1) 2010 Gerotto (B8) 2019; 180 Marczak (B19) 2020; 9 Mitula (B22) 2015; 56 Park (B30) 2015; 520 Sterling (B37) 2015; 55 Pagadala (B28) 2017; 9 Cutler (B4) 2010; 61 Nishimura (B25) 2009; 326 Ludwikow (B18) 2014; 7 Saez (B33) 2006; 141 Saez (B34) 2008; 20 Rodriguez (B31) 2015; 20 Soon (B36) 2012; 335 Takeuchi (B39) 2016; 6 Zhu (B47) 2016; 167 Gotoh (B10) 2015; 5 Irwin (B13) 2012; 52 Melcher (B21) 2010; 17 Cao (B3) 2017; 8 Yoshida (B46) 2006; 281 Irwin (B12) 2005; 45 Vogt (B43) 2005; 280 Luan (B16) 2003; 54 Fuchs (B7) 2013; 280 Miyazono (B24) 2009; 462 Ludwików (B17) 2009; 230 Vaidya (B41) 2017; 12 DeLano (B5) 2002 Pan (B29) 2015; 5 Kim (B14) 2011; 21 Ye (B44) 2017; 173 Yin (B45) 2009; 16 |
| References_xml | – volume-title: The PyMOL Molecular Graphics System year: 2002 ident: B5 contributor: fullname: DeLano – volume: 6 start-page: 37060 year: 2016 ident: B39 article-title: Abscinazole-E3M, a practical inhibitor of abscisic acid 8′-hydroxylase for improving drought tolerance publication-title: Sci. Rep doi: 10.1038/srep37060 contributor: fullname: Takeuchi – volume: 9 start-page: 91 year: 2017 ident: B28 article-title: Software for molecular docking: a review publication-title: Biophys. Rev doi: 10.1007/s12551-016-0247-1 contributor: fullname: Pagadala – volume: 27 start-page: 14 year: 2018 ident: B9 article-title: UCSF ChimeraX: Meeting modern challenges in visualization and analysis publication-title: Protein Sci doi: 10.1002/pro.3235 contributor: fullname: Goddard – volume: 366 start-page: eaaw8848 year: 2019 ident: B42 article-title: Dynamic control of plant water use using designed ABA receptor agonists publication-title: Science doi: 10.1126/science.aaw8848 contributor: fullname: Vaidya – year: 2010 ident: B1 article-title: Sanguinarine as a potent and specific inhibitor of protein phosphatase 2C in vitro and induces apoptosis via phosphorylation of p38 in HL60 cells publication-title: Biosci. Biotechnol. Biochem doi: 10.1271/bbb.90735 contributor: fullname: Aburai – volume: 5 start-page: 14076 year: 2015 ident: B10 article-title: Statin-activated nuclear receptor PXR promotes SGK2 dephosphorylation by scaffolding PP2C to induce hepatic gluconeogenesis publication-title: Sci. Rep doi: 10.1038/srep14076 contributor: fullname: Gotoh – volume: 9 year: 2020 ident: B19 article-title: Protein Phosphatases Type 2C Group A Interact with and Regulate the Stability of ACC Synthase 7 in Arabidopsis publication-title: Cells doi: 10.3390/cells9040978 contributor: fullname: Marczak – volume: 21 start-page: 3029 year: 2002 ident: B11 article-title: Homeodomain protein ATHB6 is a target of the protein phosphatase ABI1 and regulates hormone responses in Arabidopsis publication-title: EMBO J doi: 10.1093/emboj/cdf316 contributor: fullname: Himmelbach – volume: 462 start-page: 609 year: 2009 ident: B24 article-title: Structural basis of abscisic acid signalling publication-title: Nature doi: 10.1038/nature08583 contributor: fullname: Miyazono – volume: 520 start-page: 545 year: 2015 ident: B30 article-title: Agrochemical control of plant water use using engineered abscisic acid receptors publication-title: Nature doi: 10.1038/nature14123 contributor: fullname: Park – volume: 21 start-page: 990 year: 2011 ident: B14 article-title: Chemical genetics reveals negative regulation of abscisic acid signaling by a plant immune response pathway publication-title: Curr. Biol doi: 10.1016/j.cub.2011.04.045 contributor: fullname: Kim – volume: 230 start-page: 1003 year: 2009 ident: B17 article-title: Gene expression profiling of ozone-treated Arabidopsis abi1td insertional mutant: Protein phosphatase 2C ABI1 modulates biosynthesis ratio of ABA and ethylene publication-title: Planta doi: 10.1007/s00425-009-1001-8 contributor: fullname: Ludwików – volume: 281 start-page: 5310 year: 2006 ident: B46 article-title: The regulatory domain of SRK2E/OST1/SnRK2.6 interacts with ABI1 and integrates abscisic acid (ABA) and osmotic stress signals controlling stomatal closure in Arabidopsis publication-title: J. Biol. Chem doi: 10.1074/jbc.M509820200 contributor: fullname: Yoshida – volume: 55 start-page: 2324 year: 2015 ident: B37 article-title: ZINC 15 - Ligand Discovery for Everyone publication-title: J. Chem. Inf. Model doi: 10.1021/acs.jcim.5b00559 contributor: fullname: Sterling – volume: 180 start-page: 1582 year: 2019 ident: B8 article-title: Thylakoid protein phosphorylation dynamics in a moss mutant lacking SERINE/THREONINE PROTEIN KINASE STN8 publication-title: Plant Physiol doi: 10.1104/pp.19.00117 contributor: fullname: Gerotto – volume: 9 start-page: 236 year: 2004 ident: B35 article-title: Plant PP2C phosphatases: Emerging functions in stress signaling publication-title: Trends Plant Sci doi: 10.1016/j.tplants.2004.03.007 contributor: fullname: Schweighofer – volume: 25 start-page: 844 year: 2020 ident: B15 article-title: Drug Discovery for Thirsty Crops publication-title: Trends Plant Sci doi: 10.1016/j.tplants.2020.07.001 contributor: fullname: Lozano-Juste – volume: 54 start-page: 63 year: 2003 ident: B16 article-title: Protein phosphatases in plants publication-title: Annu. Rev. Plant Biol doi: 10.1146/annurev.arplant.54.031902.134743 contributor: fullname: Luan – volume: 20 start-page: 330 year: 2015 ident: B31 article-title: Unnatural agrochemical ligands for engineered abscisic acid receptors publication-title: Trends Plant Sci doi: 10.1016/j.tplants.2015.04.001 contributor: fullname: Rodriguez – volume: 17 start-page: 1102 year: 2010 ident: B21 article-title: Identification and mechanism of ABA receptor antagonism publication-title: Nat. Struct. Mol. Biol doi: 10.1038/nsmb.1887 contributor: fullname: Melcher – volume: 326 start-page: 1373 year: 2009 ident: B25 article-title: Structural mechanism of abscisic acid binding and signaling by dimeric PYR1 publication-title: Science doi: 10.1126/science.1181829 contributor: fullname: Nishimura – volume: 56 start-page: 2351 year: 2015 ident: B22 article-title: Arabidopsis ABA-Activated Kinase MAPKKK18 is Regulated by Protein Phosphatase 2C ABI1 and the Ubiquitin-Proteasome Pathway publication-title: Plant Cell Physiol. doi: 10.1093/pcp/pcv146 contributor: fullname: Mitula – volume: 280 start-page: 19078 year: 2005 ident: B43 article-title: The benzo[c]phenanthridine alkaloid, sanguinarine, is a selective, cell-active inhibitor of mitogen-activated protein kinase phosphatase-1 publication-title: J. Biol. Chem doi: 10.1074/jbc.M501467200 contributor: fullname: Vogt – volume: 280 start-page: 681 year: 2013 ident: B7 article-title: Type 2C protein phosphatases in plants publication-title: FEBS J doi: 10.1111/j.1742-4658.2012.08670.x contributor: fullname: Fuchs – volume: 110 start-page: 12132 year: 2013 ident: B27 article-title: Activation of dimeric ABA receptors elicits guard cell closure, ABA-regulated gene expression, and drought tolerance publication-title: Proc. Natl. Acad. Sci. U. S. A. doi: 10.1073/pnas.1305919110 contributor: fullname: Okamoto – volume: 51 start-page: 1821 year: 2010 ident: B40 article-title: Molecular basis of the core regulatory network in ABA responses: Sensing, signaling and transport publication-title: Plant Cell Physiol doi: 10.1093/pcp/pcq156 contributor: fullname: Umezawa – volume: 61 start-page: 651 year: 2010 ident: B4 article-title: Abscisic Acid: Emergence of a Core Signaling Network publication-title: Annu. Rev. Plant Biol doi: 10.1146/annurev-arplant-042809-112122 contributor: fullname: Cutler – volume: 169 start-page: 1469 year: 2015 ident: B6 article-title: Posttranslational protein modifications in plant metabolism publication-title: Plant Physiol doi: 10.1104/pp.15.01378 contributor: fullname: Friso – volume: 52 start-page: 1757 year: 2012 ident: B13 article-title: ZINC: A free tool to discover chemistry for biology publication-title: J. Chem. Inf. Model doi: 10.1021/ci3001277 contributor: fullname: Irwin – volume: 16 start-page: 1230 year: 2009 ident: B45 article-title: Structural insights into the mechanism of abscisic acid signaling by PYL proteins publication-title: Nat. Struct. Mol. Biol doi: 10.1038/nsmb.1730 contributor: fullname: Yin – volume: 20 start-page: 2972 year: 2008 ident: B34 article-title: HAB1-SWI3B interaction reveals a link between abscisic acid signaling and putative SWI/SNF chromatin-remodeling complexes in Arabidopsis publication-title: Plant Cell doi: 10.1105/tpc.107.056705 contributor: fullname: Saez – volume: 167 start-page: 313 year: 2016 ident: B47 article-title: Abiotic Stress Signaling and Responses in Plants publication-title: Cell doi: 10.1016/j.cell.2016.08.029 contributor: fullname: Zhu – volume: 160 start-page: 379 year: 2012 ident: B2 article-title: Unique drought resistance functions of the highly ABA-induced clade a protein phosphatase 2Cs publication-title: Plant Physiol doi: 10.1104/pp.112.202408 contributor: fullname: Bhaskara – volume: 141 start-page: 1389 year: 2006 ident: B33 article-title: Enhancement of abscisic acid sensitivity and reduction of water consumption in Arabidopsis by combined inactivation of the protein phosphatases type 2C ABI1 and HAB1 publication-title: Plant Physiol doi: 10.1104/pp.106.081018 contributor: fullname: Saez – volume: 335 start-page: 85 year: 2012 ident: B36 article-title: Molecular mimicry regulates ABA signaling by SnRK2 kinases and PP2C phosphatases publication-title: Science doi: 10.1126/science.1215106 contributor: fullname: Soon – volume: 18 start-page: 259 year: 2013 ident: B23 article-title: Structure and function of abscisic acid receptors publication-title: Trends Plant Sci doi: 10.1016/j.tplants.2012.11.002 contributor: fullname: Miyakawa – volume: 462 start-page: 602 year: 2009 ident: B20 article-title: A gate-latch-lock mechanism for hormone signalling by abscisic acid receptors publication-title: Nature doi: 10.1038/nature08613 contributor: fullname: Melcher – volume: 61 start-page: 290 year: 2010 ident: B26 article-title: PYR/PYL/RCAR family members are major in-vivo ABI1 protein phosphatase 2C-interacting proteins in Arabidopsis publication-title: Plant J doi: 10.1111/j.1365-313X.2009.04054.x contributor: fullname: Nishimura – volume: 173 start-page: 2356 year: 2017 ident: B44 article-title: A novel chemical inhibitor of ABA signaling targets all ABA receptors publication-title: Plant Physiol doi: 10.1104/pp.16.01862 contributor: fullname: Ye – volume: 7 start-page: 960 year: 2014 ident: B18 article-title: Arabidopsis Protein Phosphatase 2C ABI1 Interacts with Type i ACC Synthases and Is Involved in the Regulation of Ozone-Induced Ethylene Biosynthesis publication-title: Mol. Plant doi: 10.1093/mp/ssu025 contributor: fullname: Ludwikow – volume: 365 start-page: 23 year: 2007 ident: B38 article-title: Small-molecule inhibitors of ser/thr protein phosphatases: Specificity, use and common forms of abuse publication-title: Methods Mol. Biol doi: 10.1385/1-59745-267-X:23 contributor: fullname: Swingle – volume: 8 start-page: 1183 year: 2017 ident: B3 article-title: Combining chemical and genetic approaches to increase drought resistance in plants publication-title: Nat. Commun doi: 10.1038/s41467-017-01239-3 contributor: fullname: Cao – volume: 45 start-page: 177 year: 2005 ident: B12 article-title: ZINC - A free database of commercially available compounds for virtual screening publication-title: J. Chem. Inf. Model doi: 10.1021/ci049714+ contributor: fullname: Irwin – volume: 5 start-page: 8560 year: 2015 ident: B29 article-title: The catalytic role of the M2 metal ion in PP2Cα publication-title: Sci. Rep doi: 10.1038/srep08560 contributor: fullname: Pan – volume: 49 start-page: 1658 year: 2006 ident: B32 article-title: Discovery of protein phosphatase 2C inhibitors by virtual screening publication-title: J. Med. Chem doi: 10.1021/jm051033y contributor: fullname: Rogers – volume: 12 start-page: 2842 year: 2017 ident: B41 article-title: A rationally designed agonist defines subfamily IIIA ABA receptors as critical targets for manipulating transpiration publication-title: ACS Chem. Biol. doi: 10.1021/acschembio.7b00650 contributor: fullname: Vaidya |
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| SubjectTerms | Plant Science PP2C inhibitor protein phosphatase 2C group A protein-ligand complexes structure-based virtual screening |
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| Title | Identification of Novel Inhibitors of a Plant Group A Protein Phosphatase Type 2C Using a Combined In Silico and Biochemical Approach |
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