ENGINEERED PRIMATE L-METHIONINASE FOR THERAPEUTIC PURPOSES

摘要

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.

主权项

1. An isolated, modified primate cystathionine-γ-lyase (CGL) enzyme having at least one substitution relative to a native primate CGL amino acid sequence (see SEQ ID NOs: 1 and 7-10), said at least one substitution including a substitution at position 59, 63, 91, 119, 268, 331, 339, and/or 353 of the native primate CGL sequence, wherein the at least one substitution cannot be only Val at position 59, Asn at position 59, Leu at position 119, and/or Val at position 339.