2fk2: Difference between revisions
New page: left|200px<br /> <applet load="2fk2" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fk2, resolution 1.65Å" /> '''Structure of the Al... |
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'''Structure of the Alzheimer's Amyloid Precursor Protein (APP) Copper Binding Domain in 'small unit cell' form, Cu(I)-bound'''<br /> | '''Structure of the Alzheimer's Amyloid Precursor Protein (APP) Copper Binding Domain in 'small unit cell' form, Cu(I)-bound'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
2FK2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CU1 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 2FK2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CU1:'>CU1</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FK2 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: cu(i) coordination]] | [[Category: cu(i) coordination]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:25:29 2008'' | ||
Revision as of 18:25, 15 February 2008
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Structure of the Alzheimer's Amyloid Precursor Protein (APP) Copper Binding Domain in 'small unit cell' form, Cu(I)-bound
OverviewOverview
Alzheimer's disease (AD) is the major cause of dementia. Amyloid beta, peptide (Abeta), generated by proteolytic cleavage of the amyloid, precursor protein (APP), is central to AD pathogenesis. APP can function, as a metalloprotein and modulate copper (Cu) transport, presumably via its, extracellular Cu-binding domain (CuBD). Cu binding to the CuBD reduces, Abeta levels, suggesting that a Cu mimetic may have therapeutic potential., We describe here the atomic structures of apo CuBD from three crystal, forms and found they have identical Cu-binding sites despite the different, crystal lattices. The structure of Cu(2+)-bound CuBD reveals that the, metal ligands are His147, His151, Tyr168 and two water molecules, which, are arranged in a square pyramidal geometry. The site resembles a Type 2, non-blue Cu center and is supported by electron paramagnetic resonance and, extended X-ray absorption fine structure studies. A previous study, suggested that Met170 might be a ligand but we suggest that this residue, plays a critical role as an electron donor in CuBDs ability to reduce Cu, ions. The structure of Cu(+)-bound CuBD is almost identical to the, Cu(2+)-bound structure except for the loss of one of the water ligands., The geometry of the site is unfavorable for Cu(+), thus providing a, mechanism by which CuBD could readily transfer Cu ions to other proteins.
DiseaseDisease
Known diseases associated with this structure: Alzheimer disease-1, APP-related OMIM:[104760], Amyloidosis, cerebroarterial, Dutch type OMIM:[104760], Amyloidosis, cerebroarterial, Iowa type OMIM:[104760], Blood group, P system OMIM:[607922]
About this StructureAbout this Structure
2FK2 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structural Studies of the Alzheimer's Amyloid Precursor Protein Copper-binding Domain Reveal How it Binds Copper Ions., Kong GK, Adams JJ, Harris HH, Boas JF, Curtain CC, Galatis D, Masters CL, Barnham KJ, McKinstry WJ, Cappai R, Parker MW, J Mol Biol. 2007 Mar 16;367(1):148-61. Epub 2006 Dec 21. PMID:17239395
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