Interaction of Cisplatin
with Human Superoxide Dismutase
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Abstract
<i>cis</i>-Diamminedichloroplatinum(II) (cisplatin)
is
able to interact with human superoxide dismutase (hSOD1) in the disulfide
oxidized apo form with a dissociation constant of 37 ± 3 μM
through binding cysteine 111 (Cys111) located at the edge of the subunit
interface. It also binds to Cu<sub>2</sub>–Zn<sub>2</sub> and
Zn<sub>2</sub>–Zn<sub>2</sub> forms of hSOD1. Cisplatin inhibits
aggregation of demetalated oxidized hSOD1, and it is further able
to dissolve and monomerize oxidized hSOD1 oligomers <i>in vitro</i> and <i>in cell</i>, thus indicating its potential as a
leading compound for amyotrophic lateral sclerosis