Subunit asymmetry in the three‐dimensional structure of a human CuZnSOD mutant found in familial amyotrophic lateral sclerosis

The X‐ray crystal structure of a human copper/zinc superoxide dismutase mutant (G37R CuZnSOD) found in some patients with the inherited form of Lou Gehrig's disease (FALS) has been determined to 1.9 Å resolution. The two SOD subunits have distinct environments in the crystal and are different in structure at their copper binding sites. One subunit (subunitintact) shows a four‐coordinate ligand geometry of the copper ion, whereas the other subunit (subunitbroken) shows a three‐coordinate geometry of the copper ion. Also, subunitintact, displays higher atomic displacement parameters for backbone atoms ( = 30 ± 10 Å2) than subunitbroken ( = 24 ± 11 Å2). This structure is the first CuZnSOD to show large differences between the two subunits. Factors that may contribute to these differences are discussed and a possible link of a looser structure to FALS is suggested.

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