Molecular basis for human aquaporin inhibition

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Molecular basis for human aquaporin inhibition. / Huang, Peng; Åbacka, Hannah; Wilson, Carter J; Wind, Malene Lykke; Rűtzler, Michael; Hagström-Andersson, Anna; Gourdon, Pontus; de Groot, Bert L; Venskutonytė, Raminta; Lindkvist-Petersson, Karin.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 121, No. 7, e2319682121, 2024.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Huang, P, Åbacka, H, Wilson, CJ, Wind, ML, Rűtzler, M, Hagström-Andersson, A, Gourdon, P, de Groot, BL, Venskutonytė, R & Lindkvist-Petersson, K 2024, 'Molecular basis for human aquaporin inhibition', Proceedings of the National Academy of Sciences of the United States of America, vol. 121, no. 7, e2319682121. https://doi.org/10.1073/pnas.2319682121

APA

Huang, P., Åbacka, H., Wilson, C. J., Wind, M. L., Rűtzler, M., Hagström-Andersson, A., Gourdon, P., de Groot, B. L., Venskutonytė, R., & Lindkvist-Petersson, K. (2024). Molecular basis for human aquaporin inhibition. Proceedings of the National Academy of Sciences of the United States of America, 121(7), [e2319682121]. https://doi.org/10.1073/pnas.2319682121

Vancouver

Huang P, Åbacka H, Wilson CJ, Wind ML, Rűtzler M, Hagström-Andersson A et al. Molecular basis for human aquaporin inhibition. Proceedings of the National Academy of Sciences of the United States of America. 2024;121(7). e2319682121. https://doi.org/10.1073/pnas.2319682121

Author

Huang, Peng ; Åbacka, Hannah ; Wilson, Carter J ; Wind, Malene Lykke ; Rűtzler, Michael ; Hagström-Andersson, Anna ; Gourdon, Pontus ; de Groot, Bert L ; Venskutonytė, Raminta ; Lindkvist-Petersson, Karin. / Molecular basis for human aquaporin inhibition. In: Proceedings of the National Academy of Sciences of the United States of America. 2024 ; Vol. 121, No. 7.

Bibtex

@article{d9c5ae08383344a8b08633c9d5a8a870,
title = "Molecular basis for human aquaporin inhibition",
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-{\AA} 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.",
keywords = "Humans, Aquaporins/metabolism, Neoplasms, Aquaporin 1/metabolism",
author = "Peng Huang and Hannah {\AA}backa and Wilson, {Carter J} and Wind, {Malene Lykke} and Michael R{\H u}tzler and Anna Hagstr{\"o}m-Andersson and Pontus Gourdon and {de Groot}, {Bert L} and Raminta Venskutonytė and Karin Lindkvist-Petersson",
year = "2024",
doi = "10.1073/pnas.2319682121",
language = "English",
volume = "121",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "7",

}

RIS

TY - JOUR

T1 - Molecular basis for human aquaporin inhibition

AU - Huang, Peng

AU - Åbacka, Hannah

AU - Wilson, Carter J

AU - Wind, Malene Lykke

AU - Rűtzler, Michael

AU - Hagström-Andersson, Anna

AU - Gourdon, Pontus

AU - de Groot, Bert L

AU - Venskutonytė, Raminta

AU - Lindkvist-Petersson, Karin

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - Humans

KW - Aquaporins/metabolism

KW - Neoplasms

KW - Aquaporin 1/metabolism

U2 - 10.1073/pnas.2319682121

DO - 10.1073/pnas.2319682121

M3 - Journal article

C2 - 38319972

VL - 121

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 7

M1 - e2319682121

ER -

ID: 390240739