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Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors.

ABSTRACT: 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.

SUBMITTER: Gusach A

PROVIDER: S-EPMC6897958 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors.

Gusach Anastasiia A Luginina Aleksandra A Marin Egor E Brouillette Rebecca L RL Besserer-Offroy Élie É Longpré Jean-Michel JM Ishchenko Andrii A Popov Petr P Patel Nilkanth N Fujimoto Taku T Maruyama Toru T Stauch Benjamin B Ergasheva Margarita M Romanovskaia Daria D Stepko Anastasiia A Kovalev Kirill K Shevtsov Mikhail M Gordeliy Valentin V Han Gye Won GW Katritch Vsevolod V Borshchevskiy Valentin V Sarret Philippe P Mishin Alexey A Cherezov Vadim V

Nature communications 20191206 1

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 ...[more]

PMID: 31811124

Dataset Information

Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors.

Publications

Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors.

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