Sandbox Reserved 713 - Revision history

Andréa Mc Cann at 19:02, 6 January 2013

Andréa Mc Cann — Sun, 06 Jan 2013 19:02:09 GMT

←Older revision		Revision as of 19:02, 6 January 2013
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	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 state is not favorable and can lead to the tranfert of the Cu (I) to others proteins.In Fig.2 standard atomic colouring reprensents the Cu(II)binding form.		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 state is not favorable and can lead to the tranfert of the Cu (I) to others proteins.In Fig.2 standard atomic colouring reprensents the Cu(II)binding form.
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	=='''Medical Implication'''==		=='''Medical Implication'''==

Andréa Mc Cann at 19:01, 6 January 2013

Andréa Mc Cann — Sun, 06 Jan 2013 19:01:37 GMT

←Older revision		Revision as of 19:01, 6 January 2013
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	===Secondary structure===		===Secondary structure===

-	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.	+	2fkl is constituted by two chains called A and B <ref name="MolecularI"/>. Both chains have 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.

	===Tertiary structure===		===Tertiary structure===
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	Finally, quaternary structure is formed by two chain A and B, however, there are a few contacts between those two chains.		Finally, quaternary structure is formed by two chain A and B, however, there are a few contacts between those two chains.
	The strand B0 allows thanks to hydrogen bounds some of those interactions.		The strand B0 allows thanks to hydrogen bounds some of those interactions.
-	There are also some Van der Waals interaction ~~between~~ diffenents aminoacids located on the two chains such as : <br/>	+	There are also some Van der Waals interaction betweens diffenents aminoacids located on the two chains such as : <br/>
	His147 (A) and Phe135 (B) <br/>		His147 (A) and Phe135 (B) <br/>
	Gly175 (A) and Leu171 (B) <br/>		Gly175 (A) and Leu171 (B) <br/>
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	=='''Biological role'''==		=='''Biological role'''==

-	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" />	+	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 drives many biological functions of our organism. But in particular situations like overcconcentration it can also become toxic for the cell. <ref name="Molecular" />
	[[Image:CuI coordination.png \| thumb \| 220px \| left \| Fig.1: Cu(I) binding geometry]]		[[Image:CuI coordination.png \| thumb \| 220px \| left \| Fig.1: Cu(I) binding geometry]]


-	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).	+	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 (represented 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).


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-	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.	+	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 state is not favorable and can lead to the tranfert of the Cu (I) to others proteins.In Fig.2 standard atomic colouring reprensents the Cu(II)binding form.

	=='''Medical Implication'''==		=='''Medical Implication'''==

Andréa Mc Cann: /* '''Medical Implication''' */

Andréa Mc Cann — Sun, 06 Jan 2013 18:05:56 GMT

'''Medical Implication'''

←Older revision		Revision as of 18:05, 6 January 2013
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	The differents domains involved into the Aβ dimerisation aren't yet wery well known, but it seems that E1 and E2 are playing a major role. E1 contains the copper-binding site domain and also the Growth Factor-like Domain, rather than E2 contains the Central APP domain. Those two regions are located in the extracellurlar space. <ref> PMID : 20400860 </ref>		The differents domains involved into the Aβ dimerisation aren't yet wery well known, but it seems that E1 and E2 are playing a major role. E1 contains the copper-binding site domain and also the Growth Factor-like Domain, rather than E2 contains the Central APP domain. Those two regions are located in the extracellurlar space. <ref> PMID : 20400860 </ref>

-	If the CuBD (located in E1 region) does contribute to APP dimerisation without Cu ions, that ~~mean~~ that the Cu binding may reduce Aβ production, either by shifting the monomer-dimer equilibrium to favor monomer form, or by re-orienting the dimer form, which ~~disfavour~~ the Aβ production. <ref name="Molecular" />	+	If the CuBD (located in E1 region) does contribute to APP dimerisation without Cu ions, that means that the Cu binding may reduce Aβ production, either by shifting the monomer-dimer equilibrium to favor monomer form, or by re-orienting the dimer form, which disfavours the Aβ production. <ref name="Molecular" />
-		+
-		+

	=='''Additionnal Resources'''==		=='''Additionnal Resources'''==

Andréa Mc Cann: /* '''Biological role''' */

Andréa Mc Cann — Sun, 06 Jan 2013 18:03:42 GMT

'''Biological role'''

←Older revision		Revision as of 18:03, 6 January 2013
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	=='''Biological role'''==		=='''Biological role'''==

-	2FKL ~~belong~~ 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" />	+	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" />
	[[Image:CuI coordination.png \| thumb \| 220px \| left \| Fig.1: Cu(I) binding geometry]]		[[Image:CuI coordination.png \| thumb \| 220px \| left \| Fig.1: Cu(I) binding geometry]]

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	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.		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.
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	=='''Medical Implication'''==		=='''Medical Implication'''==

Andréa Mc Cann: /* Tertiary structure */

Andréa Mc Cann — Sun, 06 Jan 2013 18:02:22 GMT

Tertiary structure

←Older revision		Revision as of 18:02, 6 January 2013
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	Between the Cysteine 133 and the Cystein 187 we can find a <scene name='Sandbox_Reserved_719/Disulfide_bond/1'>disulfide bound</scene> which links <scene name='Sandbox_Reserved_713/Disulfide_brige_beta1_3/1'>the strand beta 1 and beta 3</scene> and <scene name='Sandbox_Reserved_713/Bislufide_bridge/1'>another one</scene> between cystein 158 and cystein186 which links the alpha helix to the strand Beta 3. Between the cysteine 144 and the cysteine 174 we can describe another <scene name='Sandbox_Reserved_713/Dislfide_brige_2/1'>disulfide bound</scene>.		Between the Cysteine 133 and the Cystein 187 we can find a <scene name='Sandbox_Reserved_719/Disulfide_bond/1'>disulfide bound</scene> which links <scene name='Sandbox_Reserved_713/Disulfide_brige_beta1_3/1'>the strand beta 1 and beta 3</scene> and <scene name='Sandbox_Reserved_713/Bislufide_bridge/1'>another one</scene> between cystein 158 and cystein186 which links the alpha helix to the strand Beta 3. Between the cysteine 144 and the cysteine 174 we can describe another <scene name='Sandbox_Reserved_713/Dislfide_brige_2/1'>disulfide bound</scene>.

-	In order to improve the stabilization of this structure there is a small <scene name='Sandbox_Reserved_713/Hydrophobic_core/1'>hydrophobic core</scene> which ~~contain~~ different residues from each seconday structure. (Leu 136, Trp 150, Val 153, Ala154, Leu 165, Met 170, Val 182 and Val 185)	+	In order to improve the stabilization of this structure there is a small <scene name='Sandbox_Reserved_713/Hydrophobic_core/1'>hydrophobic core</scene> which contains different residues from each seconday structure. (Leu 136, Trp 150, Val 153, Ala154, Leu 165, Met 170, Val 182 and Val 185)

	The study of the structure also showed on the surface of the Cu-Binding Site different regions <scene name='Sandbox_Reserved_713/Negatively_charged/1'>highly negatively charged</scene> (Glu 156, Glu 160, Glu 183 , Asp 167 et Asp 131 ) and <scene name='Sandbox_Reserved_713/Positively_charged/1'>positively</scene> charged(Lys 132, Lys134, Lys161, His 147, His 151 and Lys 155)		The study of the structure also showed on the surface of the Cu-Binding Site different regions <scene name='Sandbox_Reserved_713/Negatively_charged/1'>highly negatively charged</scene> (Glu 156, Glu 160, Glu 183 , Asp 167 et Asp 131 ) and <scene name='Sandbox_Reserved_713/Positively_charged/1'>positively</scene> charged(Lys 132, Lys134, Lys161, His 147, His 151 and Lys 155)

Andréa Mc Cann at 17:43, 5 January 2013

Andréa Mc Cann — Sat, 05 Jan 2013 17:43:25 GMT

←Older revision		Revision as of 17:43, 5 January 2013
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	{{STRUCTURE_2fkl\| PDB=2fkl \| SCENE= }}		{{STRUCTURE_2fkl\| PDB=2fkl \| SCENE= }}

-	[[Image:~~http://www.jbc.org/content/278/19/17401~~.~~long~~]]	+	[[Image:2fkl pymol representation.png\| thumb \| 220px \| left\| PyMol representation of 2fkl]]

	=='''Introduction'''==		=='''Introduction'''==

Andréa Mc Cann at 17:41, 5 January 2013

Andréa Mc Cann — Sat, 05 Jan 2013 17:41:38 GMT

←Older revision		Revision as of 17:41, 5 January 2013
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	{{STRUCTURE_2fkl\| PDB=2fkl \| SCENE= }}		{{STRUCTURE_2fkl\| PDB=2fkl \| SCENE= }}

-		+	[[Image:http://www.jbc.org/content/278/19/17401.long]]

	=='''Introduction'''==		=='''Introduction'''==

Andréa Mc Cann at 17:30, 5 January 2013

Andréa Mc Cann — Sat, 05 Jan 2013 17:30:24 GMT

←Older revision		Revision as of 17:30, 5 January 2013
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	2FKL belong 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" />		2FKL belong 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" />
	[[Image:CuI coordination.png \| thumb \| 220px \| left \| Fig.1: Cu(I) binding geometry]]		[[Image:CuI coordination.png \| thumb \| 220px \| left \| Fig.1: Cu(I) binding geometry]]
		+
		+
	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).		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).

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	[[Image:CuII coordination complex.jpg \| thumb \| 220px \| left\| Fig.2: Cu(I) binding geometry]]		[[Image:CuII coordination complex.jpg \| thumb \| 220px \| left\| Fig.2: Cu(I) binding geometry]]
		+
		+
	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.		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.

Andréa Mc Cann at 17:29, 5 January 2013

Andréa Mc Cann — Sat, 05 Jan 2013 17:29:42 GMT

←Older revision		Revision as of 17:29, 5 January 2013
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	[[Image:CuI coordination.png \| thumb \| 220px \| left \| Fig.1: Cu(I) binding geometry]]		[[Image:CuI coordination.png \| thumb \| 220px \| left \| Fig.1: Cu(I) binding geometry]]
	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).		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).
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	[[Image:CuII coordination complex.jpg \| thumb \| 220px \| left\| Fig.2: Cu(I) binding geometry]]		[[Image:CuII coordination complex.jpg \| thumb \| 220px \| left\| Fig.2: Cu(I) binding geometry]]
	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.		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.
		+
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		+
		+
		+
		+
		+
		+
		+
		+
		+
		+
		+

	=='''Medical Implication'''==		=='''Medical Implication'''==

Andréa Mc Cann at 17:29, 5 January 2013

Andréa Mc Cann — Sat, 05 Jan 2013 17:29:08 GMT

←Older revision		Revision as of 17:29, 5 January 2013
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	2FKL belong 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" />		2FKL belong 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" />
-	[[Image:CuI coordination.png \| thumb \| 220px \| ~~right~~ \| Fig.1: Cu(I) binding geometry]]	+	[[Image:CuI coordination.png \| thumb \| 220px \| left \| Fig.1: Cu(I) binding geometry]]
-	~~[[Image:CuII coordination complex.jpg \| thumb \| 220px \| left\| Fig.2: Cu(I) binding geometry]]~~	+
-		+
	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).		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).

		+
		+
		+	[[Image:CuII coordination complex.jpg \| thumb \| 220px \| left\| Fig.2: Cu(I) binding geometry]]
	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.		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.