2 research outputs found
A Rationally Designed Agonist Defines Subfamily IIIA Abscisic Acid Receptors As Critical Targets for Manipulating Transpiration
Increasing drought
and diminishing freshwater supplies have stimulated
interest in developing small molecules that can be used to control
transpiration. Receptors for the plant hormone abscisic acid (ABA)
have emerged as key targets for this application, because ABA controls
the apertures of stomata, which in turn regulate transpiration. Here,
we describe the rational design of cyanabactin, an ABA receptor agonist
that preferentially activates <i>Pyrabactin Resistance 1</i> (PYR1) with low nanomolar potency. A 1.63 Ã… X-ray crystallographic
structure of cyanabactin in complex with PYR1 illustrates that cyanabactin’s
arylnitrile mimics ABA’s cyclohexenone oxygen and engages the
tryptophan lock, a key component required to stabilize activated receptors.
Further, its sulfonamide and 4-methylbenzyl substructures mimic ABA’s
carboxylate and C6 methyl groups, respectively. Isothermal titration
calorimetry measurements show that cyanabactin’s compact structure
provides ready access to high ligand efficiency on a relatively simple
scaffold. Cyanabactin treatments reduce <i>Arabidopsis</i> whole-plant stomatal conductance and activate multiple ABA responses,
demonstrating that its <i>in vitro</i> potency translates
to ABA-like activity <i>in vivo</i>. Genetic analyses show
that the effects of cyanabactin, and the previously identified agonist
quinabactin, can be abolished by the genetic removal of PYR1 and PYL1,
which form subclade A within the dimeric subfamily III receptors.
Thus, cyanabactin is a potent and selective agonist with a wide spectrum
of ABA-like activities that defines subfamily IIIA receptors as key
target sites for manipulating transpiration
A Rationally Designed Agonist Defines Subfamily IIIA Abscisic Acid Receptors As Critical Targets for Manipulating Transpiration
Increasing drought
and diminishing freshwater supplies have stimulated
interest in developing small molecules that can be used to control
transpiration. Receptors for the plant hormone abscisic acid (ABA)
have emerged as key targets for this application, because ABA controls
the apertures of stomata, which in turn regulate transpiration. Here,
we describe the rational design of cyanabactin, an ABA receptor agonist
that preferentially activates <i>Pyrabactin Resistance 1</i> (PYR1) with low nanomolar potency. A 1.63 Ã… X-ray crystallographic
structure of cyanabactin in complex with PYR1 illustrates that cyanabactin’s
arylnitrile mimics ABA’s cyclohexenone oxygen and engages the
tryptophan lock, a key component required to stabilize activated receptors.
Further, its sulfonamide and 4-methylbenzyl substructures mimic ABA’s
carboxylate and C6 methyl groups, respectively. Isothermal titration
calorimetry measurements show that cyanabactin’s compact structure
provides ready access to high ligand efficiency on a relatively simple
scaffold. Cyanabactin treatments reduce <i>Arabidopsis</i> whole-plant stomatal conductance and activate multiple ABA responses,
demonstrating that its <i>in vitro</i> potency translates
to ABA-like activity <i>in vivo</i>. Genetic analyses show
that the effects of cyanabactin, and the previously identified agonist
quinabactin, can be abolished by the genetic removal of PYR1 and PYL1,
which form subclade A within the dimeric subfamily III receptors.
Thus, cyanabactin is a potent and selective agonist with a wide spectrum
of ABA-like activities that defines subfamily IIIA receptors as key
target sites for manipulating transpiration