What is an E3 ligand?

Related Products. PDF 1.2 MB. A PROTAC (Proteolysis Targeting Chimeric Molecule) is a protein degrader comprised of a ligand for E3 ligase (E3 ligase binder), a linker and a ligand for target protein (target binder).

How do Hect and RING ligases differ?

Unlike the HECT domain, the RING finger domain does not form a catalytic intermediate with ubiquitin. Instead, the RING finger serves, at a minimum, as a scaffold that brings E2 and substrate together, and at least one study suggests that RING finger domains can also allosterically activate E2s (Ozkan et al., 2005).

How is ubiquitin attached?

Ubiquitin molecules can also be linked through a peptide bond between the C-terminal glycine and the N-terminal methionine of the incoming ubiquitin molecule, forming a linear ubiquitin chain.

What is Arvinas?

Corporate Profile. Arvinas is a clinical-stage biopharmaceutical company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases through the discovery, development, and commercialization of therapies to degrade disease-causing proteins.

What is an E3 ligase?

The vast majority of E3 ligases belong to the group of really interesting new gene (RING) and RING-related E3s – such as plant homeodomain (PHD) and leukemia associated protein (LAP) finger proteins, and members of the U-box family (Deshaies and Joazeiro, 2009). These mediate the direct transfer of ubiquitin from E2 to substrate.

What is the role of E3 ubiquitin ligase in cancer?

RING-, HECT-, and RBR-type E3 Ubiquitin Ligases: Involvement in Human Cancer In the ubiquitylation system, E3 ubiquitin ligases play a key role in determining substrate specificity and catalyzing the transfer of ubiquitin from E2 enzymes to the substrate.

Are RBR E3 ligases a potential target for cancer treatment?

The recently classified RBR E3 ligases catalyze the transfer of ubiquitin by a RING/HECT hybrid-like mechanism. Notably, these ligases are also emphasized as important potential candidates for targets of cancer treatment drugs.

What is the function of HECT domain E3s?

In mammals, there are ~30 HECT domain E3s. Among their many functions, HECT E3s have prominent roles in protein trafficking, the immune response, and in several signaling pathways that regulate cellular growth and proliferation ( Rotin and Kumar, 2009 ).