3K7R
Crystal structure of [TM][CuAtx1]3
Summary for 3K7R
| Entry DOI | 10.2210/pdb3k7r/pdb |
| Descriptor | Metal homeostasis factor ATX1, COPPER (II) ION, TETRATHIOMOLYBDATE, ... (5 entities in total) |
| Functional Keywords | ferredoxin-like fold, protein-metal-drug complex, cu-mo metal cluster, chaperone, copper transport, ion transport, metal-binding, transport |
| Biological source | Saccharomyces cerevisiae (brewer's yeast,lager beer yeast,yeast) |
| Cellular location | Cytoplasm: P38636 |
| Total number of polymer chains | 12 |
| Total formula weight | 100973.51 |
| Authors | Xue, Y.,Alvarez, H.M.,Robinson, C.D.,Mondragon, A.,O'Halloran, T.V. (deposition date: 2009-10-13, release date: 2009-11-24, Last modification date: 2023-09-06) |
| Primary citation | 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 Cited by 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: 19965379DOI: 10.1126/science.1179907 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.28 Å) |
Structure validation
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