8ZTC

Crystal structure of Mps1-AMP complex

Summary for 8ZTC

• Entry DOI: 10.2210/pdb8ztc/pdb
• Descriptor: Mitogen-activated protein kinase MPS1, ADENOSINE MONOPHOSPHATE (3 entities in total)
• Functional Keywords: m. oryzae, kinase, amp, complex, signaling protein
• Biological source: Pyricularia oryzae
• Total number of polymer chains: 1
• Total formula weight: 48775.13

Authors

Kong, Z.,Li, S.,Zhang, X.,Wang, D.,Liu, J. (deposition date: 2024-06-07, release date: 2025-04-23)

Primary citation

Kong, Z.,Li, S.,Li, J.,Chen, Y.,Chen, M.,Zhang, X.,Wang, D.,Liu, J.
Combinatorial Targeting of Common Docking and ATP Binding Sites on Mps1 MAPK for Management of Pathogenic Fungi.
J.Agric.Food Chem., 72:27115-27124, 2024

PubMed Abstract: Resistance in pathogenic fungi necessitates the development of fungicides with new mechanisms of action. The Mps1 MAPK of , 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─an interaction site for its MAPKK─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.

PubMed: 39622772
DOI: 10.1021/acs.jafc.4c09504

Experimental method

X-RAY DIFFRACTION (2.26 Å)