E3 BINDING POCKETS AND IDENTIFICATION AND USE OF E3 LIGASE INHIBITORS

摘要

The present invention provides, inter alia, an isolated protein fragment that includes a binding pocket or active site on an E3 ligase that modulates the E2-E3 interface, wherein the binding pocket is defined by the capacity of residue F63 of E2 to fit within the pocket. The present invention also provides an agent that interacts with such a binding pocket on a E3 ligase. Methods for identifying an agent that may inhibit a RING-domain E3 ubiquitin ligase, methods for treating a condition in a mammal using such an agent, and methods for selectively inhibiting the ubiquitination function of an E3 ligase, are further provided.