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.
Designed abscisic acid analogs as antagonists of PYL-PP2C receptor interactions.
J. Takeuchi,Masanori Okamoto,Tomonori Akiyama,T. Muto,S. Yajima,M. Sue,M. Seo,Y. Kanno,T. Kamo,A. Endo,E. Nambara,N. Hirai,Toshiyuki Ohnishi,S. Cutler,Y. Todoroki
Published 2014 in Nature Chemical Biology
ABSTRACT
PUBLICATION RECORD
- Publication year
2014
- Venue
Nature Chemical Biology
- Publication date
2014-06-01
- Fields of study
Biology, Medicine, Chemistry
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- 3'-alkylsulfanyl aba analogs
Synthesized ABA derivatives bearing alkylsulfanyl substituents at the 3' position with different alkyl chain lengths.
Aliases: 3'-alkylsulfanyl ABAs, 3'-alkylsulfanyl analogs
- abscisic acid (aba)
A plant stress hormone used here as the parent scaffold for designing receptor antagonists.
Aliases: ABA, abscisic acid
- pp2c phosphatases
Group-A protein phosphatases 2C that are inhibited in ABA signaling when bound by ABA-activated receptors.
Aliases: group-A PP2Cs, protein phosphatases 2C
- pyl-pp2c receptor interactions
The receptor-phosphatase binding interaction that mediates ABA signal repression and is the target of the designed antagonists.
Aliases: PYL-PP2C interactions
- pyl receptors
Arabidopsis PYR/PYL/RCAR receptors that bind ABA and form the receptor side of the ABA signaling complex.
Aliases: PYR/PYL/RCAR receptors, PYL, PYR/PYL/RCAR
- receptor tunnel above the aba 3' ring ch
A structural tunnel observed in receptor-ABA complexes that lies above the ABA 3' ring CH and opens toward the PP2C-binding interface.
Aliases: tunnel above ABA's 3' ring CH, ABA tunnel
- six-carbon alkyl substitution
A six-carbon alkyl side chain attached at the 3' position of the ABA analogs.
Aliases: C6 alkyl substitution, six-carbon chain
- stress-induced aba responses
Abiotic-stress-associated physiological responses triggered by ABA signaling in vivo.
Aliases: ABA responses, stress responses
- structure-based design
A design strategy that uses structural information from receptor-ligand complexes to guide analog synthesis.
Aliases: structure-guided design
REFERENCES
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