3WG8

Crystal structure of the abscisic acid receptor PYR1 in complex with an antagonist AS6

Summary for 3WG8

• Entry DOI: 10.2210/pdb3wg8/pdb
• Descriptor: Abscisic acid receptor PYR1, (2Z,4E)-5-[(1S)-3-(hexylsulfanyl)-1-hydroxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl]-3-methylpenta-2,4-dienoic acid (3 entities in total)
• Functional Keywords: abscisic acid, hormone receptor
• Biological source: Arabidopsis thaliana (mouse-ear cress)
• Cellular location: Cytoplasm (By similarity): O49686
• Total number of polymer chains: 1
• Total formula weight: 25813.03

Authors

Akiyama, T.,Sue, M.,Takeuchi, J.,Okamoto, M.,Muto, T.,Endo, A.,Nambara, E.,Hirai, N.,Ohnishi, T.,Cutler, S.R.,Todoroki, Y.,Yajima, S. (deposition date: 2013-07-31, release date: 2014-05-07, Last modification date: 2023-11-08)

Primary citation

Takeuchi, J.,Okamoto, M.,Akiyama, T.,Muto, T.,Yajima, S.,Sue, M.,Seo, M.,Kanno, Y.,Kamo, T.,Endo, A.,Nambara, E.,Hirai, N.,Ohnishi, T.,Cutler, S.R.,Todoroki, Y.
Designed abscisic acid analogs as antagonists of PYL-PP2C receptor interactions
Nat.Chem.Biol., 10:477-482, 2014

PubMed Abstract: The plant stress hormone abscisic acid (ABA) is critical for several abiotic stress responses. ABA signaling is normally repressed by group-A protein phosphatases 2C (PP2Cs), but stress-induced ABA binds Arabidopsis PYR/PYL/RCAR (PYL) receptors, which then bind and inhibit PP2Cs. X-ray structures of several receptor-ABA complexes revealed a tunnel above ABA's 3' ring CH that opens at the PP2C binding interface. Here, ABA analogs with sufficiently long 3' alkyl chains were predicted to traverse this tunnel and block PYL-PP2C interactions. To test this, a series of 3'-alkylsulfanyl ABAs were synthesized with different alkyl chain lengths. Physiological, biochemical and structural analyses revealed that a six-carbon alkyl substitution produced a potent ABA antagonist that was sufficiently active to block multiple stress-induced ABA responses in vivo. This study provides a new approach for the design of ABA analogs, and the results validated structure-based design for this target class.

PubMed: 24792952
DOI: 10.1038/nchembio.1524

Experimental method

X-RAY DIFFRACTION (2.3 Å)