Engineered primate cystine/cysteine degrading enzymes for therapeutic uses
AssigneeBoard of Regents, The University of Texas System
InventorsGeorge Georgiou, Everett Stone, Shira Cramer
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Abstract
Methods and compositions related to the engineering of a protein with L-cyst(e)ine degrading enzyme activity are described. For example, disclosed are modified cystathionine-γ-lyases comprising one or more amino acid substitutions and capable of degrading L-cyst(e)ine. Furthermore, compositions and methods are provided for the treatment of cancer and cystinuria using the disclosed modified enzymes or nucleic acids encoding said enzymes.
Claims36
An isolated, modified primate cystathionine-γ-lyase (CGL) enzyme having the following substitutions relative to a native human CGL amino acid sequence (SEQ ID NO:
- 1), wherein the modified enzyme has both cystinase and cysteinase activity, and wherein said primate is selected from the group consisting of Homo sapiens, Pongo abelii, Pan troglodytes, Pan paniscus, and Macaca fascicularis;
- said substitutions comprising:
- a glutamic acid at position 55, a threonine at position 59, and a valine at position 339.
An isolated, modified human cystathionine-γ-lyase (CGL) enzyme having the following substitutions relative to a native human CGL amino acid sequence (SEQ ID NO:
- 1), wherein the modified enzyme has both cystinase and cysteinase activity, said substitutions comprising:
- a glutamic acid at position 55, a threonine at position 59, and a valine at position 339.
Dependencies are inferred from the claim text.