1do5: Difference between revisions
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|PDB= 1do5 |SIZE=350|CAPTION= <scene name='initialview01'>1do5</scene>, resolution 2.75Å | |PDB= 1do5 |SIZE=350|CAPTION= <scene name='initialview01'>1do5</scene>, resolution 2.75Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=ZN:ZINC ION'>ZN</scene> | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1qup|1qup]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1do5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1do5 OCA], [http://www.ebi.ac.uk/pdbsum/1do5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1do5 RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Rosenzweig, A C.]] | [[Category: Rosenzweig, A C.]] | ||
[[Category: Wernimont, A K.]] | [[Category: Wernimont, A K.]] | ||
[[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 Sun Mar 30 19:45:28 2008'' | ||
