1g73: Difference between revisions

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[[Image:1g73.gif|left|200px]]<br />

[[Image:1g73.gif|left|200px]]<br /><applet load="1g73" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="1g73" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1g73, resolution 2.0Å" />

'''CRYSTAL STRUCTURE OF SMAC BOUND TO XIAP-BIR3 DOMAIN'''<br />

==Overview==

Apoptosis is an essential process in the development and homeostasis of, all metazoans. The inhibitor-of-apoptosis (IAP) proteins suppress cell, death by inhibiting the activity of caspases; this inhibition is performed, by the zinc-binding BIR domains of the IAP proteins. The mitochondrial, protein Smac/DIABLO promotes apoptosis by eliminating the inhibitory, effect of IAPs through physical interactions. Amino-terminal sequences in, Smac/DIABLO are required for this function, as mutation of the very first, amino acid leads to loss of interaction with IAPs and concomitant loss of, Smac/DIABLO function. Here we report the high-resolution crystal structure, of Smac/DIABLO complexed with the third BIR domain (BIR3) of XIAP. Our, results show that the N-terminal four residues (Ala-Val-Pro-Ile) in, Smac/DIABLO recognize a surface groove on BIR3, with the first residue Ala, binding a hydrophobic pocket and making five hydrogen bonds to, neighbouring residues on BIR3. These observations provide a structural, explanation for the roles of the Smac N terminus as well as the conserved, N-terminal sequences in the Drosophila proteins Hid/Grim/Reaper. In, conjunction with other observations, our results reveal how Smac may, relieve IAP inhibition of caspase-9 activity. In addition to explaining a, number of biological observations, our structural analysis identifies, potential targets for drug screening.

Apoptosis is an essential process in the development and homeostasis of all metazoans. The inhibitor-of-apoptosis (IAP) proteins suppress cell death by inhibiting the activity of caspases; this inhibition is performed by the zinc-binding BIR domains of the IAP proteins. The mitochondrial protein Smac/DIABLO promotes apoptosis by eliminating the inhibitory effect of IAPs through physical interactions. Amino-terminal sequences in Smac/DIABLO are required for this function, as mutation of the very first amino acid leads to loss of interaction with IAPs and concomitant loss of Smac/DIABLO function. Here we report the high-resolution crystal structure of Smac/DIABLO complexed with the third BIR domain (BIR3) of XIAP. Our results show that the N-terminal four residues (Ala-Val-Pro-Ile) in Smac/DIABLO recognize a surface groove on BIR3, with the first residue Ala binding a hydrophobic pocket and making five hydrogen bonds to neighbouring residues on BIR3. These observations provide a structural explanation for the roles of the Smac N terminus as well as the conserved N-terminal sequences in the Drosophila proteins Hid/Grim/Reaper. In conjunction with other observations, our results reveal how Smac may relieve IAP inhibition of caspase-9 activity. In addition to explaining a number of biological observations, our structural analysis identifies potential targets for drug screening.

==Disease==

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==About this Structure==

1G73 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1G73 OCA].

1G73 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G73 OCA].

==Reference==

Line 19:

Line 18:

[[Category: Chai, J.]]

[[Category: Shi, Y.]]

[[Category: Suber, T.L.]]

[[Category: Suber, T L.]]

[[Category: Wu, G.]]

[[Category: Wu, J.W.]]

[[Category: Wu, J W.]]

[[Category: ZN]]

[[Category: helix bundle]]

[[Category: zinc-binding domain]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov~~ 12 17:01:~~19 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:46:50 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1g73.gif|left|200px]]<br />
+[[Image:1g73.gif|left|200px]]<br /><applet load="1g73" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1g73" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1g73, resolution 2.0&Aring;" />
 '''CRYSTAL STRUCTURE OF SMAC BOUND TO XIAP-BIR3 DOMAIN'''<br />
 ==Overview==
-Apoptosis is an essential process in the development and homeostasis of, all metazoans. The inhibitor-of-apoptosis (IAP) proteins suppress cell, death by inhibiting the activity of caspases; this inhibition is performed, by the zinc-binding BIR domains of the IAP proteins. The mitochondrial, protein Smac/DIABLO promotes apoptosis by eliminating the inhibitory, effect of IAPs through physical interactions. Amino-terminal sequences in, Smac/DIABLO are required for this function, as mutation of the very first, amino acid leads to loss of interaction with IAPs and concomitant loss of, Smac/DIABLO function. Here we report the high-resolution crystal structure, of Smac/DIABLO complexed with the third BIR domain (BIR3) of XIAP. Our, results show that the N-terminal four residues (Ala-Val-Pro-Ile) in, Smac/DIABLO recognize a surface groove on BIR3, with the first residue Ala, binding a hydrophobic pocket and making five hydrogen bonds to, neighbouring residues on BIR3. These observations provide a structural, explanation for the roles of the Smac N terminus as well as the conserved, N-terminal sequences in the Drosophila proteins Hid/Grim/Reaper. In, conjunction with other observations, our results reveal how Smac may, relieve IAP inhibition of caspase-9 activity. In addition to explaining a, number of biological observations, our structural analysis identifies, potential targets for drug screening.
+Apoptosis is an essential process in the development and homeostasis of all metazoans. The inhibitor-of-apoptosis (IAP) proteins suppress cell death by inhibiting the activity of caspases; this inhibition is performed by the zinc-binding BIR domains of the IAP proteins. The mitochondrial protein Smac/DIABLO promotes apoptosis by eliminating the inhibitory effect of IAPs through physical interactions. Amino-terminal sequences in Smac/DIABLO are required for this function, as mutation of the very first amino acid leads to loss of interaction with IAPs and concomitant loss of Smac/DIABLO function. Here we report the high-resolution crystal structure of Smac/DIABLO complexed with the third BIR domain (BIR3) of XIAP. Our results show that the N-terminal four residues (Ala-Val-Pro-Ile) in Smac/DIABLO recognize a surface groove on BIR3, with the first residue Ala binding a hydrophobic pocket and making five hydrogen bonds to neighbouring residues on BIR3. These observations provide a structural explanation for the roles of the Smac N terminus as well as the conserved N-terminal sequences in the Drosophila proteins Hid/Grim/Reaper. In conjunction with other observations, our results reveal how Smac may relieve IAP inhibition of caspase-9 activity. In addition to explaining a number of biological observations, our structural analysis identifies potential targets for drug screening.
 ==Disease==
@@ Line 11: / Line 10: @@
 ==About this Structure==
-G73 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1G73 OCA].
+G73 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G73 OCA].
 ==Reference==
@@ Line 19: / Line 18: @@
 [[Category: Chai, J.]]
 [[Category: Shi, Y.]]
-[[Category: Suber, T.L.]]
+[[Category: Suber, T L.]]
 [[Category: Wu, G.]]
-[[Category: Wu, J.W.]]
+[[Category: Wu, J W.]]
 [[Category: ZN]]
 [[Category: helix bundle]]
 [[Category: zinc-binding domain]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:01:19 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:46:50 2008''