5kw2
From Proteopedia
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/FFAR1_HUMAN FFAR1_HUMAN]] Receptor for medium and long chain saturated and unsaturated fatty acids. Binding of the ligand increase intracellular calcium concentration and amplify glucose-stimulated insulin secretion. The activity of this receptor is mediated by G-proteins that activate phospholipase C. Seems to act through a G(q) and G(i)-mediated pathway.<ref>PMID:12496284</ref> | [[http://www.uniprot.org/uniprot/FFAR1_HUMAN FFAR1_HUMAN]] Receptor for medium and long chain saturated and unsaturated fatty acids. Binding of the ligand increase intracellular calcium concentration and amplify glucose-stimulated insulin secretion. The activity of this receptor is mediated by G-proteins that activate phospholipase C. Seems to act through a G(q) and G(i)-mediated pathway.<ref>PMID:12496284</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Activation of free fatty acid receptor 1 (GPR40) by synthetic partial and full agonists occur via distinct allosteric sites. A crystal structure of GPR40-TAK-875 complex revealed the allosteric site for the partial agonist. Here we report the 2.76-A crystal structure of human GPR40 in complex with a synthetic full agonist, compound 1, bound to the second allosteric site. Unlike TAK-875, which acts as a Galphaq-coupled partial agonist, compound 1 is a dual Galphaq and Galphas-coupled full agonist. compound 1 binds in the lipid-rich region of the receptor near intracellular loop 2 (ICL2), in which the stabilization of ICL2 by the ligand is likely the primary mechanism for the enhanced G protein activities. The endogenous free fatty acid (FFA), gamma-linolenic acid, can be computationally modeled in this site. Both gamma-linolenic acid and compound 1 exhibit positive cooperativity with TAK-875, suggesting that this site could also serve as a FFA binding site. | ||
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| + | Structural basis for GPR40 allosteric agonism and incretin stimulation.,Ho JD, Chau B, Rodgers L, Lu F, Wilbur KL, Otto KA, Chen Y, Song M, Riley JP, Yang HC, Reynolds NA, Kahl SD, Lewis AP, Groshong C, Madsen RE, Conners K, Lineswala JP, Gheyi T, Saflor MD, Lee MR, Benach J, Baker KA, Montrose-Rafizadeh C, Genin MJ, Miller AR, Hamdouchi C Nat Commun. 2018 Apr 25;9(1):1645. doi: 10.1038/s41467-017-01240-w. PMID:29695780<ref>PMID:29695780</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5kw2" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 06:25, 9 May 2018
The extra-helical binding site of GPR40 and the structural basis for allosteric agonism and incretin stimulation
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Categories: Lysozyme | Baker, K A | Benach, J | Chau, B | Chen, Y | Conners, K | Genin, M J | Gheyi, T | Groshong, C | Hamdouchi, C | Ho, J D | Kahl, S D | Lee, M R | Lewis, A P | Linswala, J P | Lu, F | Madsen, R E | Miller, A R | Montrose-Rafizadeh, C | Otto, K A | Reynolds, N A | Riley, J P | Rodgers, L | Saflor, M D | Song, M | Wilbur, K L | Yang, H C | Fatty acid binding protein-hydrolase complex | Free fatty acid receptor 1 | G-protein coupled receptor | Lipid-binding protein
