Methods and compositions relating to the engineering of an improved proteinwith homocyst(e)inase enzyme activityare described. For example, there are disclosed modified cystathionine-Y-lyase(CGL) enzymes comprising one or more amino acidsubstitutions and capable of degrading homocysteine. Furthermore, provided arecompositions and methods for the treatment ofhomocystinuria or hyperhomocysteinemia with homocysteine depletion using thedisclosed enzymes or nucleic acids.
