Molecular basis for human aquaporin inhibition

Peng Huang, Hannah Åbacka, Carter J Wilson, Malene Lykke Wind, Michael Rűtzler, Anna Hagström-Andersson, Pontus Gourdon, Bert L de Groot, Raminta Venskutonytė, Karin Lindkvist-Petersson

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Abstract

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.

OriginalsprogEngelsk
Artikelnummere2319682121
TidsskriftProceedings of the National Academy of Sciences of the United States of America
Vol/bind121
Udgave nummer7
Antal sider8
ISSN0027-8424
DOI
StatusUdgivet - 2024

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