8ztc

Crystal structure of Mps1-AMP complex

Structural highlights

8ztc is a 1 chain structure with sequence from Pyricularia oryzae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.26Å
Ligands:	AMP
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MPS1_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 PubMed

Resistance 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

↑ Mehrabi R, Ding S, Xu JR. MADS-box transcription factor mig1 is required for infectious growth in Magnaporthe grisea. Eukaryot Cell. 2008 May;7(5):791-9. PMID:18344407 doi:10.1128/EC.00009-08
↑ Qi Z, Wang Q, Dou X, Wang W, Zhao Q, Lv R, Zhang H, Zheng X, Wang P, Zhang Z. MoSwi6, an APSES family transcription factor, interacts with MoMps1 and is required for hyphal and conidial morphogenesis, appressorial function and pathogenicity of Magnaporthe oryzae. Mol Plant Pathol. 2012 Sep;13(7):677-89. PMID:22321443 doi:10.1111/j.1364-3703.2011.00779.x
↑ Zhou T, Dagdas YF, Zhu X, Zheng S, Chen L, Cartwright Z, Talbot NJ, Wang Z. The glycogen synthase kinase MoGsk1, regulated by Mps1 MAP kinase, is required for fungal development and pathogenicity in Magnaporthe oryzae. Sci Rep. 2017 Apr 19;7(1):945. PMID:28424497 doi:10.1038/s41598-017-01006-w
↑ Zhang X, Liu W, Li Y, Li G, Xu JR. Expression of HopAI interferes with MAP kinase signalling in Magnaporthe oryzae. Environ Microbiol. 2017 Oct;19(10):4190-4204. PMID:28799700 doi:10.1111/1462-2920.13884
↑ Xu JR, Staiger CJ, Hamer JE. Inactivation of the mitogen-activated protein kinase Mps1 from the rice blast fungus prevents penetration of host cells but allows activation of plant defense responses. Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12713-8. PMID:9770551 doi:10.1073/pnas.95.21.12713
↑ 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. 2024 Dec 11;72(49):27115-27124. PMID:39622772 doi:10.1021/acs.jafc.4c09504

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Mehrabi R, Ding S, Xu JR. MADS-box transcription factor mig1 is required for infectious growth in Magnaporthe grisea. Eukaryot Cell. 2008 May;7(5):791-9. PMID:18344407 doi:10.1128/EC.00009-08

[2] Qi Z, Wang Q, Dou X, Wang W, Zhao Q, Lv R, Zhang H, Zheng X, Wang P, Zhang Z. MoSwi6, an APSES family transcription factor, interacts with MoMps1 and is required for hyphal and conidial morphogenesis, appressorial function and pathogenicity of Magnaporthe oryzae. Mol Plant Pathol. 2012 Sep;13(7):677-89. PMID:22321443 doi:10.1111/j.1364-3703.2011.00779.x

[3] Zhou T, Dagdas YF, Zhu X, Zheng S, Chen L, Cartwright Z, Talbot NJ, Wang Z. The glycogen synthase kinase MoGsk1, regulated by Mps1 MAP kinase, is required for fungal development and pathogenicity in Magnaporthe oryzae. Sci Rep. 2017 Apr 19;7(1):945. PMID:28424497 doi:10.1038/s41598-017-01006-w

[4] Zhang X, Liu W, Li Y, Li G, Xu JR. Expression of HopAI interferes with MAP kinase signalling in Magnaporthe oryzae. Environ Microbiol. 2017 Oct;19(10):4190-4204. PMID:28799700 doi:10.1111/1462-2920.13884

[5] Xu JR, Staiger CJ, Hamer JE. Inactivation of the mitogen-activated protein kinase Mps1 from the rice blast fungus prevents penetration of host cells but allows activation of plant defense responses. Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12713-8. PMID:9770551 doi:10.1073/pnas.95.21.12713

[6] 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. 2024 Dec 11;72(49):27115-27124. PMID:39622772 doi:10.1021/acs.jafc.4c09504

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8ztc

Crystal structure of Mps1-AMP complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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