2FMA
Structure of the Alzheimer's Amyloid Precursor Protein (APP) Copper Binding Domain in 'small unit cell' form, atomic resolution
Summary for 2FMA
| Entry DOI | 10.2210/pdb2fma/pdb |
| Related | 1OWT 2FJZ 2FK1 2FK2 2FK3 2FKL |
| Descriptor | Amyloid beta A4 protein precursor, GLYCEROL (3 entities in total) |
| Functional Keywords | alpha-beta two-layered sandwich, metal binding protein |
| Biological source | Homo sapiens (human) |
| Cellular location | Membrane; Single-pass type I membrane protein: P05067 |
| Total number of polymer chains | 1 |
| Total formula weight | 6941.02 |
| Authors | Kong, G.K.-W. (deposition date: 2006-01-08, release date: 2007-01-16, Last modification date: 2024-10-09) |
| Primary citation | Kong, G.K.,Adams, J.J.,Cappai, R.,Parker, M.W. Structure of Alzheimer's disease amyloid precursor protein copper-binding domain at atomic resolution. Acta Crystallogr.,Sect.F, 63:819-824, 2007 Cited by PubMed Abstract: Amyloid precursor protein (APP) plays a central role in the pathogenesis of Alzheimer's disease, as its cleavage generates the Abeta peptide that is toxic to cells. APP is able to bind Cu2+ and reduce it to Cu+ through its copper-binding domain (CuBD). The interaction between Cu2+ and APP leads to a decrease in Abeta production and to alleviation of the symptoms of the disease in mouse models. Structural studies of CuBD have been undertaken in order to better understand the mechanism behind the process. Here, the crystal structure of CuBD in the metal-free form determined to ultrahigh resolution (0.85 A) is reported. The structure shows that the copper-binding residues of CuBD are rather rigid but that Met170, which is thought to be the electron source for Cu2+ reduction, adopts two different side-chain conformations. These observations shed light on the copper-binding and redox mechanisms of CuBD. The structure of CuBD at atomic resolution provides an accurate framework for structure-based design of molecules that will deplete Abeta production. PubMed: 17909280DOI: 10.1107/S1744309107041139 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (0.85 Å) |
Structure validation
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