8C9H

AQP7_inhibitor

Summary for 8C9H

• Entry DOI: 10.2210/pdb8c9h/pdb
• EMDB information: 15528 16510
• Descriptor: Aquaporin-7, ethyl 4-[(4-pyrazol-1-ylphenyl)methylcarbamoylamino]benzoate (2 entities in total)
• Functional Keywords: aquaglyceroporin, glycerol channel, dimer of tetramers, inhibitor, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 8
• Total formula weight: 301030.34

Authors

Huang, P.,Venskutonyte, R.,Gourdon, P.,Lindkvist-Petersson, K. (deposition date: 2023-01-22, release date: 2024-01-31, Last modification date: 2024-03-06)

Primary citation

Huang, P.,Abacka, H.,Wilson, C.J.,Wind, M.L.,Rutzler, M.,Hagstrom-Andersson, A.,Gourdon, P.,de Groot, B.L.,Venskutonyte, R.,Lindkvist-Petersson, K.
Molecular basis for human aquaporin inhibition.
Proc.Natl.Acad.Sci.USA, 121:e2319682121-e2319682121, 2024

PubMed 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.

PubMed: 38319972
DOI: 10.1073/pnas.2319682121

Experimental method

ELECTRON MICROSCOPY (3.2 Å)