Structural Basis of ABA Perception by PYR/PYL/RCAR Receptors - Abscisic Acid: Metabolism, Transport and Signaling - page 127

respectively, facilitating the ligand locate inside to the binding pocket through
water-mediated hydrogen bonds. Third, the bromo-naphthalene ring resembles
the 2,6,6-trimethyl-cyclohexene ring of ABA, which makes hydrophobic interac-
tion with the hydrophobic residues of the gate loop to induce a closed conforma-
tion (Hao et al. 2010 ) (see Fig. 7.10 a). Therefore, changing the pyridyl ring or
the bromo-naphthalene ring is the general principle in designing function ABA
analog.
As we all know, the salt bridge between the carboxylate of ABA and the
amine group of the conserved Lys in PYLs (except for PYL13) is essential for
ABA binding. Due to the lack of this salt bridge, lower efficacy of the PYL1-
pyrabactin-mediated PP2Cs inhibition compared with that of ABA was found.
Thus, modification of some function groups on pyrabactin may affect the binding
efficacies of the ligands (Hao et al. 2010 ). First, by altering the nitrogen position
on the pyridyl ring or adding some groups to the pyridyl ring, it would not form
hydrogen bonds with the polar residues or other residues in PYLs, so the syn-
thetic ABA analog could not locate into the binding pocket, thus altering the bind-
ing between PYLs and PP2Cs. Second, modifying some chemical groups in the
bromo-naphthalene ring, it would affect the binding of the gate loop to the ligand;
thus, the gate closes properly or not, so further influencing the binding with down-
stream PP2Cs.
All these mentioned above are established on the structural analysis. In order
to build up the mechanism of synthetic ABA analog, we need more knowledge of
synthetic chemistry to guide.
7.6 Other Receptors, Other Hormones
Previous reports have shown that ABA perception happens at different sites
in cells, such as plasma membrane and cytoplasm; thus, ABA receptors need to
locate in different sites (Hamilton et al. 2000 ; Levchenko et al. 2005 ). So, there
may exist other ABA receptors except for PYLs.
A report identified a G protein-coupled receptor (GPCR) homologue, GCR2,
with a K d (dissociation constant) value of 2.1 nM to bind ABA. Binding of ABA
to GCR2 results in release of the G protein and dissociation of the G ʱʲʳ hetero-
trimeric complex to activate downstream ABA effectors and to trigger the ABA
responses (Liu et al. 2007 ). However, GCR2 has been controversial with respect
to the reproducibility of ABA-related phenotypes (Gao et al. 2007 ). No published
reports from other groups to date have independently reproduced the experimental
results. On the other hand, GCR2 lacks the typical seven transmembrane domain
of GPCRs by bioinformatics analysis.
Second, GPCR-type G proteins GTG1 and GTG2 have nine predicted trans-
membrane domains, are localized at the plasma membrane. GTG1 and GTG2 both
have specific GTP-binding ability and GTPase activities. They can both bind spe-
cifically to the natural S-ABA stereoisomer in a saturable manner with K d values