PDBsum entry 3f72

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protein metals Protein-protein interface(s) links
DNA binding protein, gene regulation PDB id
Protein chains
107 a.a. *
100 a.a. *
_NA ×5
Waters ×142
* Residue conservation analysis
PDB id:
Name: DNA binding protein, gene regulation
Title: Crystal structure of the staphylococcus aureus pi258 cadc metal binding site 2 mutant
Structure: Cadmium efflux system accessory protein. Chain: a, b, c, d, e, f. Engineered: yes. Mutation: yes
Source: Staphylococcus aureus. Organism_taxid: 1280. Expressed in: escherichia coli. Expression_system_taxid: 562
2.31Å     R-factor:   0.240     R-free:   0.288
Authors: A.Kandegedara,S.Thiyagarajan,K.C.Kondapalli,T.L.Stemmler, B.P.Rosen
Key ref:
A.Kandegedara et al. (2009). Role of bound Zn(II) in the CadC Cd(II)/Pb(II)/Zn(II)-responsive repressor. J Biol Chem, 284, 14958-14965. PubMed id: 19286656 DOI: 10.1074/jbc.M809179200
07-Nov-08     Release date:   07-Apr-09    
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Protein chains
Pfam   ArchSchema ?
P20047  (CADC_STAAU) -  Cadmium resistance transcriptional regulatory protein CadC
122 a.a.
107 a.a.*
Protein chains
Pfam   ArchSchema ?
P20047  (CADC_STAAU) -  Cadmium resistance transcriptional regulatory protein CadC
122 a.a.
100 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 6 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   1 term 
  Biological process     response to cadmium ion   3 terms 
  Biochemical function     DNA binding     3 terms  


DOI no: 10.1074/jbc.M809179200 J Biol Chem 284:14958-14965 (2009)
PubMed id: 19286656  
Role of bound Zn(II) in the CadC Cd(II)/Pb(II)/Zn(II)-responsive repressor.
A.Kandegedara, S.Thiyagarajan, K.C.Kondapalli, T.L.Stemmler, B.P.Rosen.
The Staphylococcus aureus plasmid pI258 cadCA operon encodes a P-type ATPase, CadA, that confers resistance to Cd(II)/Pb(II)/Zn(II). Expression is regulated by CadC, a homodimeric repressor that dissociates from the cad operator/promoter upon binding of Cd(II), Pb(II), or Zn(II). CadC is a member of the ArsR/SmtB family of metalloregulatory proteins. The crystal structure of CadC shows two types of metal binding sites, termed Site 1 and Site 2, and the homodimer has two of each. Site 1 is the physiological inducer binding site. The two Site 2 metal binding sites are formed at the dimerization interface. Site 2 is not regulatory in CadC but is regulatory in the homologue SmtB. Here the role of each site was investigated by mutagenesis. Both sites bind either Cd(II) or Zn(II). However, Site 1 has higher affinity for Cd(II) over Zn(II), and Site 2 prefers Zn(II) over Cd(II). Site 2 is not required for either derepression or dimerization. The crystal structure of the wild type with bound Zn(II) and of a mutant lacking Site 2 was compared with the SmtB structure with and without bound Zn(II). We propose that an arginine residue allows for Zn(II) regulation in SmtB and, conversely, a glycine results in a lack of regulation by Zn(II) in CadC. We propose that a glycine residue was ancestral whether the repressor binds Zn(II) at a Site 2 like CadC or has no Site 2 like the paralogous ArsR and implies that acquisition of regulatory ability in SmtB was a more recent evolutionary event.
  Selected figure(s)  
Figure 5.
Superposition of the zinc-bound and zinc-free forms of CadC. Crystal structure of CadC Site 2 mutant (green) superposed on that of wild type CadC with Zn(II) bound in both Site 2s (purple).
Figure 6.
Comparison of the structures of SmtB and CadC with and without bound Zn(II) in Site 2. A, in SmtB, Arg^87 moves toward Site 2 upon Zn(II) binding. The backbone forms hydrogen bonds with the side chain His^117. In addition, the side chain forms hydrogen bonds with the side chain of Glu^120 and the backbone carboxyl group of His^117. B, changes in the conformation of Arg^87 influences the orientation of the first helix of the DNA binding site. C, the CadC residue corresponding to SmtB Arg^87 is Gly^84. D, interaction of Gly^84 with His^114 does not create any significant changes in the orientation of CadC helix 5. In each panel the structure in yellow is without zinc, and the structure in green is with bound zinc. The purple ball represents a zinc atom.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2009, 284, 14958-14965) copyright 2009.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20724137 Y.Kawakami, M.S.Siddiki, K.Inoue, H.Otabayashi, K.Yoshida, S.Ueda, H.Miyasaka, and I.Maeda (2010).
Application of fluorescent protein-tagged trans factors and immobilized cis elements to monitoring of toxic metals based on in vitro protein-DNA interactions.
  Biosens Bioelectron, 26, 1466-1473.  
19788177 Z.Ma, F.E.Jacobsen, and D.P.Giedroc (2009).
Coordination chemistry of bacterial metal transport and sensing.
  Chem Rev, 109, 4644-4681.  
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