Article 4YFB2 Researchers Solve Protein Structures To Fight Asthma

Researchers Solve Protein Structures To Fight Asthma

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Arthur T Knackerbracket has found the following story:

Biophysicists from the MIPT Center for Molecular Mechanisms of Aging and Age-Related Diseases have teamed up with colleagues from Canada, the U.S., Japan, France, and Germany to shed light on the structure and functioning mechanism of the CysLT receptors, which regulate inflammatory responses associated with allergic disorders. Their findings are reported in Nature Communications.

[...] As of today, the development of more effective medications for asthma and associated conditions is hindered by the lack of information on how and to what ligands the CysLT receptors bind. Their functioning mechanisms have not been clearly understood either, as this requires high-resolution structural biology data. Once these are available, researchers can proceed using computer simulations.

[...] In their recent study, researchers from the Moscow Institute of Physics and Technology identified the most critical ligand-binding determinants of the CysLT1 and CysLT2 receptors based on the structural analysis the team performed for CysLT2R and the structural data on CysLT1R published by the laboratory in October.

"The new structures have greatly improved the accuracy of ligand docking and helped us better understand the properties of ligands with respect to both receptors. Now we know how to alter drug design templates to inhibit the activity of both the CysLT1 and CysLT2 receptors or do that selectively for either of them," commented Anastasiia Gusach , a Ph.D. student at MIPT and a junior researcher at the MIPT Laboratory of Structural Biology of G Protein-Coupled Receptors.

In the future, these structures could be further developed to serve as drug candidates or tool compounds, aiding in understanding the specific role of each of the CysLT receptor subtypes in various physiological and pathological processes.

[...] This implies that with the rapid development of genome sequencing technologies and the accumulation of large volumes of statistical data, structure-function studies will not only allow accurate prediction of disease for every patient but will also enable predicting drug efficacy and improving patient safety based on how these variations in genes affect the response to certain medications.

More information: Anastasiia Gusach et al. Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors, Nature Communications (2019). DOI: 10.1038/s41467-019-13348-2

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