2XJK: Monomeric Human Cu,Zn Superoxide dismutase

How coordination of metal ions modulates protein structures is not only important for elucidating biological function but has also emerged as a key determinant in protein turnover and protein-misfolding diseases. In this study, we show that the coordination of Zn(2+) to the ALS-associated enzyme Cu/Zn superoxide dismutase (SOD1) is directly controlled by the protein's folding pathway. Zn(2+) first catalyzes the folding reaction by coordinating transiently to the Cu ligands of SOD1, which are all contained within the folding nucleus. Then, after the global folding transition has commenced, the Zn(2+) ion transfers to the higher affinity Zn site, which structures only very late in the folding process. Here it remains dynamically coordinated with an off rate of approximately 10(-5) s(-1). This relatively rapid equilibration of metals in and out of the SOD1 structure provides a simple explanation for how the exceptionally long lifetime, >100 years, of holoSOD1 is still compatible with cellular turnover: if a dissociated Zn(2+) ion is prevented from rebinding to the SOD1 structure then the lifetime of the protein is reduced to a just a few hours.
PDB ID: 2XJKDownload
MMDB ID: 84516
PDB Deposition Date: 2010/7/7
Updated in MMDB: 2010/10
Experimental Method:
x-ray diffraction
Resolution: 1.45  Å
Source Organism:
Similar Structures:
Biological Unit for 2XJK: monomeric; determined by author and by software (PISA)
Molecular Components in 2XJK
Label Count Molecule
Protein (1 molecule)
Superoxide Dismutase [cu-zn](Gene symbol: SOD1)
Molecule annotation
Chemicals (5 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB