Engineered primate L-methioninase for therapeutic purposes
AssigneeBoard of Regents, The University of Texas System
InventorsGeorge Georgiou, Everett Stone, Wei-Cheng Lu
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Abstract
Methods and compositions relating to the engineering of an improved protein with methionine-γ-lyase enzyme activity are described. For example, in certain aspects there may be disclosed a modified cystathionine-γ-lyase (CGL) comprising one or more amino acid substitutions and capable of degrading methionine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with methionine depletion using the disclosed proteins or nucleic acids.
Claims19
An isolated, modified human cystathionine-γ-lyase (CGL) enzyme having at least the following substitutions relative to a native human CGL amino acid sequence (see SEQ ID NO:
- 1), said substitutions selected from (a) E59N, S63L, L91M, R119L, K268R, T311G, E339V and I353S;
- (b) E59I, S63L, L91M, R119L, K268R, T311G, E339V and I353S;
- (c) E59N, S63L, L91M, R119A, K268R, T311G, E339V and I353S;
- and (d) E59I, S63L, L91M, R119A, K268R, T311G, E339V and I353S.
Dependencies are inferred from the claim text.