Specific active site inhibitors of enzymes or substrate binding partners and methods of producing same
AssigneeThe Governing Council of the University of Toronto
InventorsSachdev Sidhu, Linda Beatty, Andreas Ernst
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Abstract
The present disclosure provides a method of producing enzyme-specific inhibitors or substrate binding partners comprising: identifying active site residues of the substrate in the enzyme substrate complex or in substrate binding partner-substrate complex; randomizing the active site residues to produce a combinatorial library of substrate variants; and selecting substrate variants that inhibit enzyme activity or bind substrate as substrate-specific binding partners. The present disclosure also provides ubiquitin enzyme specific inhibitors and ubiquitin variants that bind ubiquitin interaction motifs.
Claims11
1-76. (canceled)
A specific inhibitor of a deubiquitinating enzyme, wherein the deubiquitinating enzyme is USP21, and wherein the inhibitor of USP21 is a ubiquitin variant comprising the amino acid sequence set forth in any of SEQ ID NO:
- 5, 6, or 7.
Dependencies are inferred from the claim text.