PDBsum entry 2fma

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protein ligands links
Metal binding protein PDB id
Protein chain
59 a.a. *
Waters ×115
* Residue conservation analysis
PDB id:
Name: Metal binding protein
Title: Structure of the alzheimer's amyloid precursor protein (app) binding domain in 'small unit cell' form, atomic resolution
Structure: Amyloid beta a4 protein precursor. Chain: a. Fragment: copper binding domain(residues 133-189). Synonym: amyloid precursor protein, amyloid beta a4 protein app-alpha, soluble app-beta. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: pichia pastoris. Expression_system_taxid: 4922.
0.85Å     R-factor:   0.131     R-free:   0.150
Authors: G.K.-W.Kong
Key ref: G.K.Kong et al. (2007). Structure of Alzheimer's disease amyloid precursor protein copper-binding domain at atomic resolution. Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 819-824. PubMed id: 17909280
08-Jan-06     Release date:   16-Jan-07    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P05067  (A4_HUMAN) -  Amyloid beta A4 protein
770 a.a.
59 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     nervous system development   1 term 
  Biochemical function     heparin binding     2 terms  


Acta Crystallogr Sect F Struct Biol Cryst Commun 63:819-824 (2007)
PubMed id: 17909280  
Structure of Alzheimer's disease amyloid precursor protein copper-binding domain at atomic resolution.
G.K.Kong, J.J.Adams, R.Cappai, M.W.Parker.
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.