4OH2

Crystal Structure of Cu/Zn Superoxide Dismutase I149T

4OH2 の概要

• エントリーDOI: 10.2210/pdb4oh2/pdb
• 分子名称: Superoxide dismutase [Cu-Zn], COPPER (II) ION, ZINC ION, ... (4 entities in total)
• 機能のキーワード: oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : P00441
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 158963.30

構造登録者

Crane, B.R.,Merz, G.E. (登録日: 2014-01-16, 公開日: 2014-10-15, 最終更新日: 2017-11-22)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.384 Å)