1DO5

HUMAN COPPER CHAPERONE FOR SUPEROXIDE DISMUTASE DOMAIN II

Summary for 1DO5

• Entry DOI: 10.2210/pdb1do5/pdb
• Related: 1qup
• Descriptor: HUMAN COPPER CHAPERONE FOR SUPEROXIDE DISMUTASE DOMAIN II, ZINC ION (3 entities in total)
• Functional Keywords: beta-barrel, chaperone
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: O14618
• Total number of polymer chains: 4
• Total formula weight: 65429.87

Authors

Lamb, A.L.,Wernimont, A.K.,Pufahl, R.A.,O'Halloran, T.V.,Rosenzweig, A.C. (deposition date: 1999-12-18, release date: 2000-12-18, Last modification date: 2024-10-16)

Primary citation

Lamb, A.L.,Wernimont, A.K.,Pufahl, R.A.,O'Halloran, T.V.,Rosenzweig, A.C.
Crystal structure of the second domain of the human copper chaperone for superoxide dismutase.
Biochemistry, 39:1589-1595, 2000

PubMed Abstract: 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.

PubMed: 10677207
DOI: 10.1021/bi992822i

Experimental method

X-RAY DIFFRACTION (2.75 Å)