2XJL

Monomeric Human Cu,Zn Superoxide dismutase without Cu ligands

Summary for 2XJL

• Entry DOI: 10.2210/pdb2xjl/pdb
• Related: 1AZV 1BA9 1DSW 1FUN 1HL4 1HL5 1KMG 1L3N 1MFM 1N18 1N19 1OEZ 1OZT 1OZU 1P1V 1PTZ 1PU0 1RK7 1SOS 1SPD 1UXL 1UXM 2AF2 2C9S 2C9U 2C9V 2V0A 2VR6 2VR7 2VR8 2WKO 2WYT 2WYZ 2WZ0 2WZ5 2WZ6 2XJK 4SOD
• Descriptor: SUPEROXIDE DISMUTASE [CU-ZN], ZINC ION, DI(HYDROXYETHYL)ETHER, ... (6 entities in total)
• Functional Keywords: oxidoreductase, cu/zn sod1, metal-binding, neurodegeneration
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm : P00441
• Total number of polymer chains: 1
• Total formula weight: 16137.00

Authors

Saraboji, K.,Leinartaite, L.,Nordlund, A.,Oliveberg, M.,Logan, D.T. (deposition date: 2010-07-07, release date: 2010-09-01, Last modification date: 2024-11-06)

Primary citation

Leinartaite, L.,Saraboji, K.,Nordlund, A.,Logan, D.T.,Oliveberg, M.
Folding Catalysis by Transient Coordination of Zn2+ to the Cu Ligands of the Als-Associated Enzyme Cu/Zn Superoxide Dismutase 1.
J.Am.Chem.Soc., 132:13495-, 2010

PubMed Abstract: 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 ∼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.

PubMed: 20822138
DOI: 10.1021/JA1057136

Experimental method

X-RAY DIFFRACTION (1.55 Å)