| Structural highlights
Disease
CLTR2_HUMAN Uveal melanoma.
Function
C562_ECOLX Electron-transport protein of unknown function.CLTR2_HUMAN Receptor for cysteinyl leukotrienes. The response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Stimulation by BAY u9773, a partial agonist, induces specific contractions of pulmonary veins and might also have an indirect role in the relaxation of the pulmonary vascular endothelium. The rank order of affinities for the leukotrienes is LTC4 = LTD4 >> LTE4.
Publication Abstract from PubMed
Cysteinyl leukotriene G protein-coupled receptors CysLT1 and CysLT2 regulate pro-inflammatory responses associated with allergic disorders. While selective inhibition of CysLT1R has been used for treating asthma and associated diseases for over two decades, CysLT2R has recently started to emerge as a potential drug target against atopic asthma, brain injury and central nervous system disorders, as well as several types of cancer. Here, we describe four crystal structures of CysLT2R in complex with three dual CysLT1R/CysLT2R antagonists. The reported structures together with the results of comprehensive mutagenesis and computer modeling studies shed light on molecular determinants of CysLTR ligand selectivity and specific effects of disease-related single nucleotide variants.
Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors.,Gusach A, Luginina A, Marin E, Brouillette RL, Besserer-Offroy E, Longpre JM, Ishchenko A, Popov P, Patel N, Fujimoto T, Maruyama T, Stauch B, Ergasheva M, Romanovskaia D, Stepko A, Kovalev K, Shevtsov M, Gordeliy V, Han GW, Katritch V, Borshchevskiy V, Sarret P, Mishin A, Cherezov V Nat Commun. 2019 Dec 6;10(1):5573. doi: 10.1038/s41467-019-13348-2. PMID:31811124[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gusach A, Luginina A, Marin E, Brouillette RL, Besserer-Offroy E, Longpre JM, Ishchenko A, Popov P, Patel N, Fujimoto T, Maruyama T, Stauch B, Ergasheva M, Romanovskaia D, Stepko A, Kovalev K, Shevtsov M, Gordeliy V, Han GW, Katritch V, Borshchevskiy V, Sarret P, Mishin A, Cherezov V. Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors. Nat Commun. 2019 Dec 6;10(1):5573. doi: 10.1038/s41467-019-13348-2. PMID:31811124 doi:http://dx.doi.org/10.1038/s41467-019-13348-2
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