2af2
From Proteopedia
(New page: 200px<br /> <applet load="2af2" size="450" color="white" frame="true" align="right" spinBox="true" caption="2af2" /> '''Solution structure of disulfide reduced and...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2af2.gif|left|200px]]<br /> | + | [[Image:2af2.gif|left|200px]]<br /><applet load="2af2" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2af2" size=" | + | |
caption="2af2" /> | caption="2af2" /> | ||
'''Solution structure of disulfide reduced and copper depleted Human Superoxide Dismutase'''<br /> | '''Solution structure of disulfide reduced and copper depleted Human Superoxide Dismutase'''<br /> | ||
==Overview== | ==Overview== | ||
| - | SOD1 has to undergo several post-translational modifications before | + | SOD1 has to undergo several post-translational modifications before reaching its mature form. The protein requires insertion of zinc and copper atoms, followed by the formation of a conserved S-S bond between Cys-57 and Cys-146 (human numbering), which makes the protein fully active. In this report an NMR structural investigation of the reduced SH-SH form of thermostable E,Zn-as-SOD1 (E is empty; as is C6A, C111S) is reported, characterizing the protein just before the last step leading to the mature form. The structure is compared with that of the oxidized S-S form as well as with that of the yeast SOD1 complexed with its copper chaperone, CCS. Local conformational rearrangements upon disulfide bridge reduction are localized in the region near Cys-57 that is completely exposed to the solvent in the present structure, at variance with the oxidized forms. There is a local disorder around Cys-57 that may serve for protein-protein recognition and may possibly be involved in intermolecular S-S bonds in familial amyotrophic lateral sclerosis-related SOD1 mutants. The structure allows us to further discuss the copper loading mechanism in SOD1. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2AF2 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 ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Superoxide_dismutase Superoxide dismutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.15.1.1 1.15.1.1] Full crystallographic information is available from [http:// | + | 2AF2 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=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Superoxide_dismutase Superoxide dismutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.15.1.1 1.15.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AF2 OCA]. |
==Reference== | ==Reference== | ||
| Line 18: | Line 17: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Superoxide dismutase]] | [[Category: Superoxide dismutase]] | ||
| - | [[Category: Amelio, N | + | [[Category: Amelio, N D.]] |
[[Category: Banci, L.]] | [[Category: Banci, L.]] | ||
[[Category: Bertini, I.]] | [[Category: Bertini, I.]] | ||
[[Category: Cantini, F.]] | [[Category: Cantini, F.]] | ||
[[Category: Gaggelli, E.]] | [[Category: Gaggelli, E.]] | ||
| - | [[Category: SPINE, Structural | + | [[Category: SPINE, Structural Proteomics in Europe.]] |
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: copper depleted protein]] | [[Category: copper depleted protein]] | ||
| Line 35: | Line 34: | ||
[[Category: structural proteomics in europe]] | [[Category: structural proteomics in europe]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:26:44 2008'' |
Revision as of 14:26, 21 February 2008
|
Solution structure of disulfide reduced and copper depleted Human Superoxide Dismutase
Contents |
Overview
SOD1 has to undergo several post-translational modifications before reaching its mature form. The protein requires insertion of zinc and copper atoms, followed by the formation of a conserved S-S bond between Cys-57 and Cys-146 (human numbering), which makes the protein fully active. In this report an NMR structural investigation of the reduced SH-SH form of thermostable E,Zn-as-SOD1 (E is empty; as is C6A, C111S) is reported, characterizing the protein just before the last step leading to the mature form. The structure is compared with that of the oxidized S-S form as well as with that of the yeast SOD1 complexed with its copper chaperone, CCS. Local conformational rearrangements upon disulfide bridge reduction are localized in the region near Cys-57 that is completely exposed to the solvent in the present structure, at variance with the oxidized forms. There is a local disorder around Cys-57 that may serve for protein-protein recognition and may possibly be involved in intermolecular S-S bonds in familial amyotrophic lateral sclerosis-related SOD1 mutants. The structure allows us to further discuss the copper loading mechanism in SOD1.
Disease
Known disease associated with this structure: Amyotrophic lateral sclerosis, due to SOD1 deficiency OMIM:[147450]
About this Structure
2AF2 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Superoxide dismutase, with EC number 1.15.1.1 Full crystallographic information is available from OCA.
Reference
Human SOD1 before harboring the catalytic metal: solution structure of copper-depleted, disulfide-reduced form., Banci L, Bertini I, Cantini F, D'Amelio N, Gaggelli E, J Biol Chem. 2006 Jan 27;281(4):2333-7. Epub 2005 Nov 14. PMID:16291742
Page seeded by OCA on Thu Feb 21 16:26:44 2008
Categories: Homo sapiens | Single protein | Superoxide dismutase | Amelio, N D. | Banci, L. | Bertini, I. | Cantini, F. | Gaggelli, E. | SPINE, Structural Proteomics in Europe. | ZN | Copper depleted protein | Disulfide bond reduced | Homodimeric protein | Human superoxide dismutase | Nmr | Solution structure | Spine | Structural genomics | Structural proteomics in europe
