1do5
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The human copper chaperone for superoxide dismutase (hCCS) delivers the | + | The human copper chaperone for superoxide dismutase (hCCS) delivers the essential copper ion cofactor to copper,zinc superoxide dismutase (SOD1), a key enzyme in antioxidant defense. Mutations in SOD1 are linked to familial amyotrophic lateral sclerosis (FALS), a fatal neurodegenerative disorder. The molecular mechanisms by which SOD1 is recognized and activated by hCCS are not understood. To better understand this biochemical pathway, we have determined the X-ray structure of the largest domain of hCCS (hCCS Domain II) to 2. 75 A resolution. The overall structure is closely related to that of its target enzyme SOD1, consisting of an eight-stranded beta-barrel and a zinc-binding site formed by two extended loops. The first of these loops provides the ligands to a bound zinc ion, and is analogous to the zinc subloop in SOD1. The second structurally resembles the SOD1 electrostatic channel loop, but lacks many of the residues important for catalysis. Like SOD1 and yCCS, hCCS forms a dimer using a highly conserved interface. In contrast to SOD1, however, the hCCS structure does not contain a copper ion bound in the catalytic site. Notably, the structure reveals a single loop proximal to the dimer interface which is unique to the CCS chaperones. |
==Disease== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Halloran, T | + | [[Category: Halloran, T V.O.]] |
| - | [[Category: Lamb, A | + | [[Category: Lamb, A L.]] |
| - | [[Category: Pufahl, R | + | [[Category: Pufahl, R A.]] |
| - | [[Category: Rosenzweig, A | + | [[Category: Rosenzweig, A C.]] |
| - | [[Category: Wernimont, A | + | [[Category: Wernimont, A K.]] |
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: beta-barrel]] | [[Category: beta-barrel]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:18:38 2008'' |
Revision as of 10:18, 21 February 2008
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HUMAN COPPER CHAPERONE FOR SUPEROXIDE DISMUTASE DOMAIN II
Contents |
Overview
The human copper chaperone for superoxide dismutase (hCCS) delivers the essential copper ion cofactor to copper,zinc superoxide dismutase (SOD1), a key enzyme in antioxidant defense. Mutations in SOD1 are linked to familial amyotrophic lateral sclerosis (FALS), a fatal neurodegenerative disorder. The molecular mechanisms by which SOD1 is recognized and activated by hCCS are not understood. To better understand this biochemical pathway, we have determined the X-ray structure of the largest domain of hCCS (hCCS Domain II) to 2. 75 A resolution. The overall structure is closely related to that of its target enzyme SOD1, consisting of an eight-stranded beta-barrel and a zinc-binding site formed by two extended loops. The first of these loops provides the ligands to a bound zinc ion, and is analogous to the zinc subloop in SOD1. The second structurally resembles the SOD1 electrostatic channel loop, but lacks many of the residues important for catalysis. Like SOD1 and yCCS, hCCS forms a dimer using a highly conserved interface. In contrast to SOD1, however, the hCCS structure does not contain a copper ion bound in the catalytic site. Notably, the structure reveals a single loop proximal to the dimer interface which is unique to the CCS chaperones.
Disease
Known disease associated with this structure: Asthma, susceptibility to OMIM:[192020]
About this Structure
1DO5 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of the second domain of the human copper chaperone for superoxide dismutase., Lamb AL, Wernimont AK, Pufahl RA, O'Halloran TV, Rosenzweig AC, Biochemistry. 2000 Feb 22;39(7):1589-95. PMID:10677207
Page seeded by OCA on Thu Feb 21 12:18:38 2008
