4OH2

Crystal Structure of Cu/Zn Superoxide Dismutase I149T

Summary for 4OH2

• Entry DOI: 10.2210/pdb4oh2/pdb
• Descriptor: Superoxide dismutase [Cu-Zn], COPPER (II) ION, ZINC ION, ... (4 entities in total)
• Functional Keywords: oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P00441
• Total number of polymer chains: 10
• Total formula weight: 158963.30

Authors

Crane, B.R.,Merz, G.E. (deposition date: 2014-01-16, release date: 2014-10-15, Last modification date: 2024-11-27)

Primary citation

Merz, G.E.,Borbat, P.P.,Pratt, A.J.,Getzoff, E.D.,Freed, J.H.,Crane, B.R.
Copper-Based Pulsed Dipolar ESR Spectroscopy as a Probe of Protein Conformation Linked to Disease States.
Biophys.J., 107:1669-1674, 2014

PubMed Abstract: We demonstrate the ability of pulsed dipolar electron spin resonance (ESR) spectroscopy (PDS) to report on the conformation of Cu-Zn superoxide dismutase (SOD1) through the sensitive measurement of dipolar interactions between inherent Cu(2+) ions. Although the extent and the anisotropy of the Cu ESR spectrum provides challenges for PDS, Ku-band (17.3 GHz) double electron-electron resonance and double-quantum coherence variants of PDS coupled with distance reconstruction methods recover Cu-Cu distances in good agreement with crystal structures. Moreover, Cu-PDS measurements expose distinct differences between the conformational properties of wild-type SOD1 and a single-residue variant (I149T) that leads to the disease amyotrophic lateral sclerosis (ALS). The I149T protein displays a broader Cu-Cu distance distribution within the SOD1 dimer compared to wild-type. In a nitroxide (NO)-labeled sample, distance distributions obtained from Cu-Cu, Cu-NO, and NO-NO separations reveal increased structural heterogeneity within the protein and a tendency for mutant dimers to associate. In contrast, perturbations caused by the ALS mutation are completely masked in the crystal structure of I149T. Thus, PDS readily detects alterations in metalloenzyme solution properties not easily deciphered by other methods and in doing so supports the notion that increased range of motion and associations of SOD1 ALS variants contribute to disease progression.

PubMed: 25296320
DOI: 10.1016/j.bpj.2014.07.068

Experimental method

X-RAY DIFFRACTION (2.384 Å)