Molecular basis for human aquaporin inhibition

Huang, Peng; Abacka, Hannah; Wilson, Carter J.; Wind, Malene Lykke; Rutzler, Michael; Hagstroem-Andersson, Anna; Gourdon, Pontus; de Groot, Bert L.; Venskutonyte, Raminta; Lindkvist-Petersson, Karin

doi:10.1073/pnas.2319682121

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Molecular basis for human aquaporin inhibition

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Wilson, Carter J.
Research Group of Computational Biomolecular Dynamics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;
Department of Theoretical and Computational Biophysics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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de Groot, Bert L.
Research Group of Computational Biomolecular Dynamics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;
Department of Theoretical and Computational Biophysics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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huang-et-al-2024
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引用

Huang, P., Abacka, H., Wilson, C. J., Wind, M. L., Rutzler, M., Hagstroem-Andersson, A., Gourdon, P., de Groot, B. L., Venskutonyte, R., & Lindkvist-Petersson, K. (2024). Molecular basis for human aquaporin inhibition. PNAS, 121(7):. doi:10.1073/pnas.2319682121.

引用: https://hdl.handle.net/21.11116/0000-000F-0E55-3

要旨

Cancer invasion and metastasis are known to be potentiated by the expression of aquaporins (AQPs). Likewise, the expression levels of AQPs have been shown to be prognostic for survival in patients and have a role in tumor growth, edema, angiogenesis, and tumor cell migration. Thus, AQPs are key players in cancer biology and potential targets for drug development. Here, we present the single-particle cryo-EM structure of human AQP7 at 3.2-Å resolution in complex with the specific inhibitor compound Z433927330. The structure in combination with MD simulations shows that the inhibitor binds to the endofacial side of AQP7. In addition, cancer cells treated with Z433927330 show reduced proliferation. The data presented here serve as a framework for the development of AQP inhibitors.