Abstract:
:Changing environmental conditions and lessening fresh water supplies have sparked intense interest in understanding and manipulating abscisic acid (ABA) signaling, which controls adaptive responses to drought and other abiotic stressors. We recently discovered a selective ABA agonist, pyrabactin, and used it to discover its primary target PYR1, the founding member of the PYR/PYL family of soluble ABA receptors. To understand pyrabactin's selectivity, we have taken a combined structural, chemical and genetic approach. We show that subtle differences between receptor binding pockets control ligand orientation between productive and nonproductive modes. Nonproductive binding occurs without gate closure and prevents receptor activation. Observations in solution show that these orientations are in rapid equilibrium that can be shifted by mutations to control maximal agonist activity. Our results provide a robust framework for the design of new agonists and reveal a new mechanism for agonist selectivity.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Peterson FC,Burgie ES,Park SY,Jensen DR,Weiner JJ,Bingman CA,Chang CE,Cutler SR,Phillips GN Jr,Volkman BFdoi
10.1038/nsmb.1898subject
Has Abstractpub_date
2010-09-01 00:00:00pages
1109-13issue
9eissn
1545-9993issn
1545-9985pii
nsmb.1898journal_volume
17pub_type
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