Human-enzyme mediated depletion of homocysteine for treating patients with hyperhomocysteinemia and homocystinuria
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 homocyst(e)inase enzyme activity are described. For example, there are disclosed modified cystathionine-γ-lyase (CGL) enzymes comprising one or more amino acid substitutions and capable of degrading homocyst(e)ine. Furthermore, provided are compositions and methods for the treatment of homocystinuria or hyperhomocysteinemia with homocyst(e)ine depletion using the disclosed enzymes or nucleic acids.
Claims16
A nucleic acid comprising a nucleotide sequence encoding a modified primate cystathionine-γ-lyase (CGL) enzyme comprising substitutions relative to a native human CGL amino acid sequence as shown in SEQ ID NO:
- 1, wherein the modified enzyme has both homocystinase and homocysteinase activity, wherein the modified enzyme comprises a sequence at least 95% identical to SEQ ID NO:
- 1, said substitutions comprising isoleucine at position 59, leucine at position 63, methionine at position 91, aspartic acid at position 119, arginine at position 268, glycine at position 311, valine at position 339, and serine at position 353.
Dependencies are inferred from the claim text.