Crystal structure of the second domain of the human copper chaperone for superoxide dismutase.

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Lamb AL, Wernimont AK, Pufahl RA, O'Halloran TV, Rosenzweig AC

Crystal structure of the second domain of the human copper chaperone for superoxide dismutase.

Biochemistry. 2000 Feb 22;39(7):1589-95.

PubMed ID
10677207 [ View in 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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Zinc chlorideCopper chaperone for superoxide dismutaseProteinHumans
Unknown
Cofactor
Details
Zinc sulfate, unspecified formCopper chaperone for superoxide dismutaseProteinHumans
Unknown
Cofactor
Details
Polypeptides
NameUniProt ID
Copper chaperone for superoxide dismutaseO14618Details