6RZ8

Crystal structure of the human cysteinyl leukotriene receptor 2 in complex with ONO-2080365

Summary for 6RZ8

• Entry DOI: 10.2210/pdb6rz8/pdb
• Descriptor: Cysteinyl leukotriene receptor 2,Soluble cytochrome b562,Cysteinyl leukotriene receptor 2, (2~{S})-8-[[4-[4-[2,3-bis(fluoranyl)phenoxy]butoxy]-2-fluoranyl-phenyl]carbonylamino]-4-(4-oxidanyl-4-oxidanylidene-but yl)-2,3-dihydro-1,4-benzoxazine-2-carboxylic acid, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, ... (5 entities in total)
• Functional Keywords: gpcr, lcp, membrane protein, cysteinyl leukotriene, cyslt2, cysltr2, cyslt2r, asthma, bril, cysteinyl leukotriene receptor 2
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 1
• Total formula weight: 51011.30

Authors

Gusach, A.,Luginina, A.,Marin, E.,Brouillette, R.L.,Besserer-Offroy, E.,Longpre, J.M.,Ishchenko, A.,Popov, P.,Fujimoto, T.,Maruyama, T.,Stauch, B.,Ergasheva, M.,Romanovskaya, D.,Stepko, A.,Kovalev, K.,Shevtsov, M.,Gordeliy, V.,Han, G.W.,Sarret, P.,Katritch, V.,Borshchevskiy, V.,Mishin, A.,Cherezov, V. (deposition date: 2019-06-12, release date: 2019-12-11, Last modification date: 2024-01-24)

Primary citation

Gusach, A.,Luginina, A.,Marin, E.,Brouillette, R.L.,Besserer-Offroy, E.,Longpre, J.M.,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, G.W.,Katritch, V.,Borshchevskiy, V.,Sarret, P.,Mishin, A.,Cherezov, V.
Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors.
Nat Commun, 10:5573-5573, 2019

PubMed Abstract: Cysteinyl leukotriene G protein-coupled receptors CysLT and CysLT regulate pro-inflammatory responses associated with allergic disorders. While selective inhibition of CysLTR has been used for treating asthma and associated diseases for over two decades, CysLTR 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 CysLTR in complex with three dual CysLTR/CysLTR 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.

PubMed: 31811124
DOI: 10.1038/s41467-019-13348-2

Experimental method

X-RAY DIFFRACTION (2.7 Å)