METHODS FOR IDENTIFYING PROTEINS AND COMPOUNDS THAT MODULATE THE ACTIVITY OF OTUB1
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Apr 14, 2014
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Apr 19, 2013
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Abstract
The present invention describes that OTUB1 cleavage of K48 poly-ubiquitin is stimulated by a select subset of E2 enzymes, and that this stimulation is regulated by the ubiquitin-charged state of the E2 and free ubiquitin. Structural and biochemical studies of OTUB1 and UBCH5B show that the E2 stimulates binding of the polyubiquitin substrate by contacting the OTUB1 N-terminal ubiquitin-binding helix. Methods for identifying E2 enzymes which stimulate or inhibit cleavage of K48 polyubiquitin, as well as novel target compounds which modulate this interaction are provided.
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