8ztc
From Proteopedia
Crystal structure of Mps1-AMP complex
Structural highlights
FunctionMPS1_PYROR Mitogen-activated protein kinase; part of the MCK1-MKK2-MPS1 MAP kinase (MAPK) signal transduction cascade that is essential for cell wall integrity and plant infection, but not for plant defense responses (PubMed:18344407, PubMed:22321443, PubMed:28424497, PubMed:28799700, PubMed:9770551). Beside its role in pathogenesis, the MPS1 cascade is active in conidiation and cellular stress responses (PubMed:9770551). Targets downstream of the MPS1-MAPK pathway include transcription factors MIG1 and SWI6, as well as GSK1 and MPG1 (PubMed:18344407, PubMed:22321443, PubMed:28424497).[1] [2] [3] [4] [5] Publication Abstract from PubMedResistance in pathogenic fungi necessitates the development of fungicides with new mechanisms of action. The Mps1 MAPK of Magnaporthe oryzae, the pathogen of rice blast disease, has been shown to be a molecular target for fungicide research. Here, we present compound TAK-733 that interacts with the common docking (CD) site of Mps1 and can be used in combination with ATP-competitive inhibitors. We initially identified compounds PLX-4720 and TAK-733 that interact with Mps1. Subsequent assays show that PLX-4720 is an ATP-competitive inhibitor, whereas TAK-733 binds to the CD site of Mps1 horizontal line an interaction site for its MAPKK horizontal line but not to the ATP-binding pocket as it does in the kinase MEK1. In vivo assays demonstrated that TAK-733 exhibits combinational effects with ATP-competitive inhibitors PLX-4720 and A378-0. Collectively, we present TAK-733 as having a new mechanism of action suitable for combinational application with ATP-competitive inhibitors in the management of pathogenic fungi. Combinatorial Targeting of Common Docking and ATP Binding Sites on Mps1 MAPK for Management of Pathogenic Fungi.,Kong Z, Li S, Li J, Chen Y, Chen M, Zhang X, Wang D, Liu J J Agric Food Chem. 2024 Dec 11;72(49):27115-27124. doi: 10.1021/acs.jafc.4c09504. , Epub 2024 Dec 2. PMID:39622772[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Large Structures | Pyricularia oryzae | Kong Z | Li S | Liu J | Wang D | Zhang X
