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protein metals Protein-protein interface(s) links
Chaperone PDB id
1do5
Jmol
Contents
Protein chains
154 a.a. *
Metals
_ZN ×4
Waters ×26
* Residue conservation analysis
PDB id:
1do5
Name: Chaperone
Title: Human copper chaperone for superoxide dismutase domain ii
Structure: Human copper chaperone for superoxide dismutase domain ii. Chain: a, b, c, d. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
Resolution:
2.75Å     R-factor:   0.228     R-free:   0.283
Authors: A.L.Lamb,A.K.Wernimont,R.A.Pufahl,T.V.O'Halloran, A.C.Rosenzweig
Key ref:
A.L.Lamb et al. (2000). Crystal structure of the second domain of the human copper chaperone for superoxide dismutase. Biochemistry, 39, 1589-1595. PubMed id: 10677207 DOI: 10.1021/bi992822i
Date:
18-Dec-99     Release date:   18-Dec-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
O14618  (CCS_HUMAN) -  Copper chaperone for superoxide dismutase
Seq:
Struc: 		274 a.a.
154 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   2 terms 
  Biochemical function     superoxide dismutase activity     2 terms  

 

 
DOI no: 10.1021/bi992822i Biochemistry 39:1589-1595 (2000)
PubMed id: 10677207  
 
 
Crystal structure of the second domain of the human copper chaperone for superoxide dismutase.
A.L.Lamb, A.K.Wernimont, R.A.Pufahl, T.V.O'Halloran, A.C.Rosenzweig.
 
  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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21258844 N.A.Veldhuis, M.J.Kuiper, R.C.Dobson, R.B.Pearson, and J.Camakaris (2011).
In silico modeling of the Menkes copper-translocating P-type ATPase 3rd metal binding domain predicts that phosphorylation regulates copper-binding.
  Biometals, 24, 477-487.  
20205585 N.J.Robinson, and D.R.Winge (2010).
Copper metallochaperones.
  Annu Rev Biochem, 79, 537-562.  
20939100 S.Kalkhof, S.Haehn, M.Paulsson, N.Smyth, J.Meiler, and A.Sinz (2010).
Computational modeling of laminin N-terminal domains using sparse distance constraints from disulfide bonds and chemical cross-linking.
  Proteins, 78, 3409-3427.  
19824702 A.K.Boal, and A.C.Rosenzweig (2009).
Structural biology of copper trafficking.
  Chem Rev, 109, 4760-4779.  
19686298 M.Islinger, K.W.Li, J.Seitz, A.Völkl, and G.H.Lüers (2009).
Hitchhiking of Cu/Zn superoxide dismutase to peroxisomes--evidence for a natural piggyback import mechanism in mammals.
  Traffic, 10, 1711-1721.  
19007184 A.N.Barry, K.M.Clark, A.Otoikhian, W.A.van der Donk, and N.J.Blackburn (2008).
Selenocysteine positional variants reveal contributions to copper binding from cysteine residues in domains 2 and 3 of human copper chaperone for superoxide dismutase.
  Biochemistry, 47, 13074-13083.  
18277979 B.E.Kim, T.Nevitt, and D.J.Thiele (2008).
Mechanisms for copper acquisition, distribution and regulation.
  Nat Chem Biol, 4, 176-185.  
16771675 Y.Furukawa, and T.V.O'Halloran (2006).
Posttranslational modifications in Cu,Zn-superoxide dismutase and mutations associated with amyotrophic lateral sclerosis.
  Antioxid Redox Signal, 8, 847-867.  
16950140 Y.Nose, B.E.Kim, and D.J.Thiele (2006).
Ctr1 drives intestinal copper absorption and is essential for growth, iron metabolism, and neonatal cardiac function.
  Cell Metab, 4, 235-244.  
15465825 C.Abajian, L.A.Yatsunyk, B.E.Ramirez, and A.C.Rosenzweig (2004).
Yeast cox17 solution structure and Copper(I) binding.
  J Biol Chem, 279, 53584-53592.
PDB codes: 1u96 1u97
12748182 L.S.Field, Y.Furukawa, T.V.O'Halloran, and V.C.Culotta (2003).
Factors controlling the uptake of yeast copper/zinc superoxide dismutase into mitochondria.
  J Biol Chem, 278, 28052-28059.  
12815046 T.B.Bartnikas, and J.D.Gitlin (2003).
Mechanisms of biosynthesis of mammalian copper/zinc superoxide dismutase.
  J Biol Chem, 278, 33602-33608.  
  12039007 S.J.Opella, T.M.DeSilva, and G.Veglia (2002).
Structural biology of metal-binding sequences.
  Curr Opin Chem Biol, 6, 217-223.  
  12039001 S.Puig, and D.J.Thiele (2002).
Molecular mechanisms of copper uptake and distribution.
  Curr Opin Chem Biol, 6, 171-180.  
11524675 A.L.Lamb, A.S.Torres, T.V.O'Halloran, and A.C.Rosenzweig (2001).
Heterodimeric structure of superoxide dismutase in complex with its metallochaperone.
  Nat Struct Biol, 8, 751-755.
PDB code: 1jk9
11473116 A.S.Torres, V.Petri, T.D.Rae, and T.V.O'Halloran (2001).
Copper stabilizes a heterodimer of the yCCS metallochaperone and its target superoxide dismutase.
  J Biol Chem, 276, 38410-38416.  
11395420 D.L.Huffman, and T.V.O'Halloran (2001).
Function, structure, and mechanism of intracellular copper trafficking proteins.
  Annu Rev Biochem, 70, 677-701.  
11524666 T.B.Bartnikas, and J.D.Gitlin (2001).
How to make a metalloprotein.
  Nat Struct Biol, 8, 733-734.  
10742187 A.C.Rosenzweig, and T.V.O'Halloran (2000).
Structure and chemistry of the copper chaperone proteins.
  Curr Opin Chem Biol, 4, 140-147.  
11101286 A.L.Lamb, A.S.Torres, T.V.O'Halloran, and A.C.Rosenzweig (2000).
Heterodimer formation between superoxide dismutase and its copper chaperone.
  Biochemistry, 39, 14720-14727.  
10858280 J.F.Eisses, J.P.Stasser, M.Ralle, J.H.Kaplan, and N.J.Blackburn (2000).
Domains I and III of the human copper chaperone for superoxide dismutase interact via a cysteine-bridged Dicopper(I) cluster.
  Biochemistry, 39, 7337-7342.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.