4BTE

DJ-1 Cu(I) complex

4BTE の概要

• エントリーDOI: 10.2210/pdb4bte/pdb
• 分子名称: PROTEIN DJ-1, COPPER (I) ION (3 entities in total)
• 機能のキーワード: hydrolase, copper chaperone, parkinson's disease, superoxide dismutase activation, multi-functional
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm: Q99497
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19980.60

構造登録者

Puno, M.R.A.,Odell, M.,Moody, P.C.E. (登録日: 2013-06-14, 公開日: 2013-11-06, 最終更新日: 2023-12-20)

主引用文献

Puno, M.R.,Patel, N.A.,Moller, S.G.,Robinson, C.V.,Moody, P.C.E.,Odell, M.
Structure of Cu(I)-Bound Dj-1 Reveals a Biscysteinate Metal Binding Site at the Homodimer Interface: Insights Into Mutational Inactivation of Dj-1 in Parkinsonism.
J.Am.Chem.Soc., 135:15974-, 2013

PubMed Abstract: The Parkinsonism-associated protein DJ-1 has been suggested to activate the Cu-Zn superoxide dismutase (SOD1) by providing its copper cofactor. The structural and chemical means by which DJ-1 could support this function is unknown. In this study, we characterize the molecular interaction of DJ-1 with Cu(I). Mass spectrometric analysis indicates binding of one Cu(I) ion per DJ-1 homodimer. The crystal structure of DJ-1 bound to Cu(I) confirms metal coordination through a docking accessible biscysteinate site formed by juxtaposed cysteine residues at the homodimer interface. Spectroscopy in crystallo validates the identity and oxidation state of the bound metal. The measured subfemtomolar dissociation constant (Kd = 6.41 × 10(-16) M) of DJ-1 for Cu(I) supports the physiological retention of the metal ion. Our results highlight the requirement of a stable homodimer for copper binding by DJ-1. Parkinsonism-linked mutations that weaken homodimer interactions will compromise this capability.

PubMed: 24144264
DOI: 10.1021/JA406010M

実験手法

X-RAY DIFFRACTION (1.38 Å)