View source for 7mlc


==PYL10 bound to the ABA pan-antagonist 4a==
<StructureSection load='7mlc' size='340' side='right'caption='[[7mlc]], [[Resolution|resolution]] 1.77&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MLC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MLC FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.77&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZLA:1-{2-[3,5-dicyclopropyl-4-(4-{[(quinoxaline-2-carbonyl)amino]methyl}-1H-1,2,3-triazol-1-yl)phenyl]acetamido}cyclohexane-1-carboxylic+acid'>ZLA</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7mlc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mlc OCA], [https://pdbe.org/7mlc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mlc RCSB], [https://www.ebi.ac.uk/pdbsum/7mlc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mlc ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Abscisic acid (ABA) is a key plant hormone that mediates both plant biotic and abiotic stress responses and many other developmental processes. ABA receptor antagonists are useful for dissecting and manipulating ABA's physiological roles in vivo. We set out to design antagonists that block receptor-PP2C interactions by modifying the agonist opabactin (OP), a synthetically accessible, high-affinity scaffold. Click chemistry was used to create an approximately 4,000-member library of C4-diversified opabactin derivatives that were screened for receptor antagonism in vitro. This revealed a peptidotriazole motif shared among hits, which we optimized to yield antabactin (ANT), a pan-receptor antagonist. An X-ray crystal structure of an ANT-PYL10 complex (1.86 A) reveals that ANT's peptidotriazole headgroup is positioned to sterically block receptor-PP2C interactions in the 4' tunnel and stabilizes a noncanonical closed-gate receptor conformer that partially opens to accommodate ANT binding. To facilitate binding-affinity studies using fluorescence polarization, we synthesized TAMRA-ANT. Equilibrium dissociation constants for TAMRA-ANT binding to Arabidopsis receptors range from approximately 400 to 1,700 pM. ANT displays improved activity in vivo and disrupts ABA-mediated processes in multiple species. ANT is able to accelerate seed germination in Arabidopsis, tomato, and barley, suggesting that it could be useful as a germination stimulant in species where endogenous ABA signaling limits seed germination. Thus, click-based diversification of a synthetic agonist scaffold allowed us to rapidly develop a high-affinity probe of ABA-receptor function for dissecting and manipulating ABA signaling.

Click-to-lead design of a picomolar ABA receptor antagonist with potent activity in vivo.,Vaidya AS, Peterson FC, Eckhardt J, Xing Z, Park SY, Dejonghe W, Takeuchi J, Pri-Tal O, Faria J, Elzinga D, Volkman BF, Todoroki Y, Mosquna A, Okamoto M, Cutler SR Proc Natl Acad Sci U S A. 2021 Sep 21;118(38). pii: 2108281118. doi:, 10.1073/pnas.2108281118. PMID:34531324<ref>PMID:34531324</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7mlc" style="background-color:#fffaf0;"></div>

==See Also==
*[[Abscisic acid receptor 3D structures|Abscisic acid receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Cutler SR]]
[[Category: Peterson FC]]
[[Category: Vaidya AS]]
[[Category: Volkman BF]]