Cryptic drug-binding sites discovered in the dance

21 November, 2022

Some of the toughest challenges in treating disease are presented by “undruggable” proteins whose structures and roles in disease are known but are seemingly unable to be targeted by drugs that will bind to them. Researchers at KAUST have now shown that the molecular motion of many “undruggable” proteins can in fact expose sites at which drugs could bind.

The research is focused on a particular molecular region, called the BTB domain, that is known to be a critical part of more than 350 proteins. It allows proteins to bind to other proteins to influence complex genetic and molecular signaling processes central to the activities of many cells.

More than 80 known BTB-containing proteins are transcription factors that control the activities of genes, a role that means many of them are implicated in cancer. As the BTB domain has proved difficult to target with drugs, these cancers are often fatal.

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Image: A KAUST-led team of researchers has revealed properties of the MIZ1 protein (illustrated above). Their findings could advance drug discovery for previously incurable diseases, including some forms of cancer. © 2022 KAUST.