3K7R

Crystal structure of [TM][CuAtx1]3

3K7R の概要

• エントリーDOI: 10.2210/pdb3k7r/pdb
• 分子名称: Metal homeostasis factor ATX1, COPPER (II) ION, TETRATHIOMOLYBDATE, ... (5 entities in total)
• 機能のキーワード: ferredoxin-like fold, protein-metal-drug complex, cu-mo metal cluster, chaperone, copper transport, ion transport, metal-binding, transport
• 由来する生物種: Saccharomyces cerevisiae (brewer's yeast,lager beer yeast,yeast)
• 細胞内の位置: Cytoplasm: P38636
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 100973.51

構造登録者

Xue, Y.,Alvarez, H.M.,Robinson, C.D.,Mondragon, A.,O'Halloran, T.V. (登録日: 2009-10-13, 公開日: 2009-11-24, 最終更新日: 2023-09-06)

主引用文献

Alvarez, H.M.,Xue, Y.,Robinson, C.D.,Canalizo-Hernandez, M.A.,Marvin, R.G.,Kelly, R.A.,Mondragon, A.,Penner-Hahn, J.E.,O'Halloran, T.V.
Tetrathiomolybdate inhibits copper trafficking proteins through metal cluster formation.
Science, 327:331-334, 2010

PubMed Abstract: Tetrathiomolybdate (TM) is an orally active agent for treatment of disorders of copper metabolism. Here we describe how TM inhibits proteins that regulate copper physiology. Crystallographic results reveal that the surprising stability of the drug complex with the metallochaperone Atx1 arises from formation of a sulfur-bridged copper-molybdenum cluster reminiscent of those found in molybdenum and iron sulfur proteins. Spectroscopic studies indicate that this cluster is stable in solution and corresponds to physiological clusters isolated from TM-treated Wilson's disease animal models. Finally, mechanistic studies show that the drug-metallochaperone inhibits metal transfer functions between copper-trafficking proteins. The results are consistent with a model wherein TM can directly and reversibly down-regulate copper delivery to secreted metalloenzymes and suggest that proteins involved in metal regulation might be fruitful drug targets.

PubMed: 19965379
DOI: 10.1126/science.1179907

実験手法

X-RAY DIFFRACTION (2.28 Å)