Sandbox Reserved 713: Difference between revisions

2fkl is constituted by two chains called A and B <ref name="MolecularI"/>. Both chains have the same length and the same organization. Each chain also contains an <scene name='Sandbox_Reserved_713/Helice_alpha/1'>alpha-helix</scene> going from residue 147 to 159 packed against a triple-strand beta sheet. The strand <scene name='Sandbox_Reserved_719/Beta1/1'>Beta1</scene> going from residue 133 to 139, the <scene name='Sandbox_Reserved_713/Beta_stream2/1'>Beta2</scene> going from residue 162 to 167, and the <scene name='Sandbox_Reserved_713/Beta_stream3/1'>Beta3</scene> going from residue 181 to 188. There is one more Beta sheet, <scene name='Sandbox_Reserved_713/Beta_0/1'>B0</scene>, formed by the residues 127 to 139 of the B chain.

There are also some Van der Waals interaction between diffenents aminoacids located on the two chains such as : <br/>

2FKL belongs to the domain of APP which is able to bind Cu and zinc. Copper is an important metal to health. It acts as an indispensable catalytic and structural cofactor that drive many biological functions of our organism. But in particular situations like overcconcentration it can also become toxic for the cell. <ref name="Molecular" />

Thanks to its extracellular Cu-Binding Domain (CuBD) constituated by the amino acids describe above, APP can modulate '''copper transport and storage'''. The Cu-binding domain of the apo protein (show in grey in the fig.1 ) seems to be able to fixe '''Cu(II) and to reduce it into Cu(I)'''. More precisely, the Tyr 168, the His 147 and the His 151 participate in Cu(II) binding but not the Methionine 170. In addition, two molecules of water, one axial and one equatorial (noted Ax and Eq on Fig.1) play an important role in <scene name='Sandbox_Reserved_713/2fk1/1'>the formation of the APP-Cu(II)complex</scene> (represented also in standard atomic colouring in Fig 1)(PDB ID : [http://www.rcsb.org/pdb/explore.do?structureId=2fk1 2fk1]). It results that the arrangement of the atoms involved in the Cu(II) binding adopts a square pyramidal geometry which can be classified as a Type 2 non-blueCu(II) center. In this type of center Cu(II) is bound by two or three nitrogene ligands and one or two oxygen ligands. Met170 is supposed to act as an electron donor to Cu(II).

In the <scene name='Sandbox_Reserved_713/2fk2_complex/1'>Cu(I) binding geometry</scene> (represented in grey in Fig.2)(PDB id [http://www.rcsb.org/pdb/explore.do?structureId=2fk2 2fk2]), there is no axial water molecules ; the site adopts also a distorted square planar arrangement which is unfavorable for Cu(I) suggesting that this states is not favorable and can lead to the tranfert of the Cu (I) to others proteins.In Fig.2 standart atomic colouring reprensents the Cu(II)binding form.