Structure-based mechanism of cysteinyl leukotriene receptor inhibition by antiasthmatic drugs.

ABSTRACT: The G protein-coupled cysteinyl leukotriene receptor CysLT₁R mediates inflammatory processes and plays a major role in numerous disorders, including asthma, allergic rhinitis, cardiovascular disease, and cancer. Selective CysLT₁R antagonists are widely prescribed as antiasthmatic drugs; however, these drugs demonstrate low effectiveness in some patients and exhibit a variety of side effects. To gain deeper understanding into the functional mechanisms of CysLTRs, we determined the crystal structures of CysLT₁R bound to two chemically distinct antagonists, zafirlukast and pranlukast. The structures reveal unique ligand-binding modes and signaling mechanisms, including lateral ligand access to the orthosteric pocket between transmembrane helices TM4 and TM5, a

SUBMITTER: Luginina A 

PROVIDER: S-EPMC6785256 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature