Structural Basis of ABA Perception by PYR/PYL/RCAR Receptors - Abscisic Acid: Metabolism, Transport and Signaling - page 126

90º, made that the napthalene ring be located too far from the gate loop of PYL2
to close it. Two hydrophobic residues Val114 and Val67 in the binding pocket of
PYL2 (corresponding to Ile110 and Ile62 in PYR1, Ile137 and Ile89 in PYL1) that
arrange the orientation of the pyrabactin are smaller than those in PYL1 or PYR1.
And the position of larger residue Ile137 in PYL1 would collide with the naph-
thalene ring of pyrabactin in the PYL2 conformation. So, these two smaller valine
residues make the naphthalene ring locate deeply in the binding pocket and far
from the gate loop. And thus the gate is unable to be closed due to the loss of its
interaction with pyrabactin (see Fig. 7.10 b).
However, the situation in PYL3 is totally different, the orientations of the naph-
thalene and pyridine ring of pyrabactin are rotated by 80° compared with those
in PYL1-pyrabactin complex. Moreover, the sulfonamide group moves to Phe81
and does not form a hydrogen bond with Lys79, while the conserved Lys residue
in other PYLs forms a hydrogen bond with the pyridyl nitrogen to locate pyra-
bactin inside to the binding pocket. Pyrabactin can induce the closure of the gate
in PYL3, but the gate loop moves further toward the binding pocket and tightly
closes the latch. On the other hand, Leu111 in PYL3 binds to pyrabactin tighter,
which also gives rise to the approach between the gate loop and the binding
pocket compared with that in PYL1, PYL2, or PYR1. So, there is no enough space
between the gate loop and the latch loop for the insertion of conserved Trp resi-
due from PP2Cs. Taken together, pyrabactin works as an antagonist for PYL3 (see
Fig. 7.10 c) (Zhang et al. 2012 ).
From the above analysis, pyrabactin is a receptor-selective ABA agonist and
antagonist. By solving the structure of the PYL1-pyrabactin-ABI1 complex, we
know that this complex resembles the structure of the PYL1-ABA-ABI1 com-
plex, in which the closure of the gate is further stabilized by the insertion of the
locking residue Trp300 of ABI1. In the ternary complex, the gate-latch interface is
tightly packed against the active site of ABI1, therefore providing a mechanism of
phosphatase inhibition (Melcher et al. 2010 ).
These different pyrabactin binding orientations in PYLs either provide or lack
Van der Waals interactions required to induce the gate closure, and these struc-
tural information shed lights on the concept of ABA receptor agonism and antago-
nism, lead to the design of pyrabactin derivatives with higher affinity and agonistic
activity.
7.5 The Outlook of Synthetic ABA Analog
By comparing pyrabactin and ( + )-ABA in their structures complexed with PYLs,
we know that these two ligands overlap with each other despite the distinct chemi-
cal structures. First, both of pyrabactin and ABA ligands are amphipathic, each
consisting of polar groups buried deep inside the pocket and hydrophobic groups
adjacent to the gate-and-latch loops. Second, the pyridyl nitrogen and the sulfona-
mide group of pyrabactin mimic the carboxylate and the hydroxyl groups of ABA,