SYNTHESIS AND CHARACTERIZATION OF A MONOMERIC MUTANT CU ZN SUPEROXIDE-DISMUTASE WITH PARTIALLY RECONSTITUTED ENZYMATIC-ACTIVITY/

A monomeric analog of human Cu/Zn superoxide dismutase (F50E/G51E SOD) , previously characterized and found to have reduced enzymic activity, was here further modified by replacing Glu133 with Gin. This substitu tion does not dramatically affect the coordination geometry at the act ive site, but enhances enzymic activity, and also increases the affini ty for anions at the active site. This behavior parallels earlier publ ished results in which this point mutation was made in the dimeric wil d-type enzyme. The analog described here has afforded for the first ti me a monomeric superoxide dismutase with substantial activity. This po int mutation does not significantly influence the protein structure bu t interactions with anions, including superoxide, are altered with res pect to the monomeric form. The present monomeric Glu133Gln mutant has partially restored enzymic activity. The diminished activity of the m onomeric analogs is discussed in the light of possible minor structura l changes and some of their characteristics are compared with those of naturally occurring mutants associated with various neurological dise ases.