PDBsum entry 2jsc

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protein metals Protein-protein interface(s) links
Transcription PDB id
Jmol PyMol
Protein chains
96 a.a. *
_CD ×2
* Residue conservation analysis
PDB id:
Name: Transcription
Title: Nmr structure of the cadmium metal-sensor cmtr from mycobact tuberculosis
Structure: Transcriptional regulator rv1994c/mt2050. Chain: a, b. Engineered: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 83332. Strain: h37rv. Atcc: 25618. Gene: rv1994c, mt2050, mtcy39.25. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 30 models
Authors: L.Banci,I.Bertini,F.Cantini,S.Ciofi-Baffoni,J.S.Cavet,C.Denn A.I.Graham,D.R.Harvie,N.J.Robinson,Structural Proteomics In (Spine)
Key ref:
L.Banci et al. (2007). NMR structural analysis of cadmium sensing by winged helix repressor CmtR. J Biol Chem, 282, 30181-30188. PubMed id: 17599915 DOI: 10.1074/jbc.M701119200
02-Jul-07     Release date:   31-Jul-07    
Go to PROCHECK summary

Protein chains
P9WMI9  (CMTR_MYCTU) -  HTH-type transcriptional regulator CmtR
118 a.a.
96 a.a.
Key:    Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     regulation of gene expression   5 terms 
  Biochemical function     cadmium ion sensor activity     7 terms  


DOI no: 10.1074/jbc.M701119200 J Biol Chem 282:30181-30188 (2007)
PubMed id: 17599915  
NMR structural analysis of cadmium sensing by winged helix repressor CmtR.
L.Banci, I.Bertini, F.Cantini, S.Ciofi-Baffoni, J.S.Cavet, C.Dennison, A.I.Graham, D.R.Harvie, N.J.Robinson.
CmtR from Mycobacterium tuberculosis is a winged helical DNA-binding repressor of the ArsR-SmtB metal-sensing family that senses cadmium and lead. Cadmium-CmtR is a dimer with the metal bound to Cys-102 from the C-terminal region of one subunit and two Cys associated with helix alphaR from the other subunit, forming a symmetrical pair of cadmium-binding sites. This is a significant novelty in the ArsR-SmtB family. The structure of the dimer could be solved at 312 K. The apoprotein at the same temperature is still a dimer, but it experiences a large conformational exchange at the dimer interface and within each monomer. This is monitored by an overall decrease of the number of nuclear Overhauser effects and by an increase of H(2)O-D(2)O exchange rates, especially at the dimeric interface, in the apo form with respect to the cadmium-bound state. The C-terminal tail region is completely unstructured in both apo and cadmium forms but becomes less mobile in the cadmium-bound protein due to the recruitment of Cys-102 as a metal-ligand. DNA binds to the apo dimer with a ratio 1:3 at millimolar concentration. Addition of cadmium to the apo-CmtR-DNA complex causes DNA detachment, restoring the NMR spectrum of free cadmium-CmtR. Cadmium binding across the dimer interface impairs DNA association by excluding the apo-conformers suited to bind DNA.
  Selected figure(s)  
Figure 1.
Solution structure of cadmium-CmtR and interaction with DNA.A, ribbon representation of dimeric cadmium-CmtR. One CmtR subunit is beige and the other sky blue (residues 10-106 are shown). Closed circles represent the flexible tail residues 106-118. B, the interaction of CmtR with DNA analyzed using ^1H-^15N HSQC spectra showing apo-CmtR (red) superimposed with apo-CmtR in the presence of DNA (blue). C, the intensities of the signals of selected backbone amide groups of apo-CmtR are plotted against the DNA/dimeric apo-CmtR ratio. The figure reports the behavior of residues belonging to both the structured region (filled symbols) and to the unstructured C-terminal region (open symbols). For each residue, all intensities have been scaled relative to the intensity observed in the absence of DNA. D, ^1H-^15N HSQC spectrum of cadmium-CmtR (red) superimposed with that of the dimeric apo-CmtR/DNA 3:1 mixture after the addition of 1 equivalent of cadmium (blue). E, ^1H-^15N HSQC spectrum of cadmium-CmtR with DNA in a 1:1 dimeric protein/DNA ratio. No chemical shift and no variation in signal intensities were observed with respect to the ^1H-^15N HSQC of free cadmium-CmtR.
Figure 3.
Dynamic properties of the C-terminal tail of CmtR.A, heteronuclear ^15N{^1H}-NOEs of residues 97-118 for apo-CmtR (hashed bars) and cadmium-CmtR (white bars). B, j(ω[H]) values of residues 97-118 for apo-CmtR (hashed bars) and cadmium-CmtR (white bars).
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 30181-30188) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20442958 D.Osman, and J.S.Cavet (2010).
Bacterial metal-sensing proteins exemplified by ArsR-SmtB family repressors.
  Nat Prod Rep, 27, 668-680.  
19290357 A.F.Peacock, O.Iranzo, and V.L.Pecoraro (2009).
Harnessing natures ability to control metal ion coordination geometry using de novo designed peptides.
  Dalton Trans, (), 2271-2280.  
19282236 A.O.Summers (2009).
Damage control: regulating defenses against toxic metals and metalloids.
  Curr Opin Microbiol, 12, 138-144.  
19456862 S.Chauhan, A.Kumar, A.Singhal, J.S.Tyagi, and H.Krishna Prasad (2009).
CmtR, a cadmium-sensing ArsR-SmtB repressor, cooperatively interacts with multiple operator sites to autorepress its transcription in Mycobacterium tuberculosis.
  FEBS J, 276, 3428-3439.  
19788177 Z.Ma, F.E.Jacobsen, and D.P.Giedroc (2009).
Coordination chemistry of bacterial metal transport and sensing.
  Chem Rev, 109, 4644-4681.  
18591244 E.Ordóñez, S.Thiyagarajan, J.D.Cook, T.L.Stemmler, J.A.Gil, L.M.Mateos, and B.P.Rosen (2008).
Evolution of metal(loid) binding sites in transcriptional regulators.
  J Biol Chem, 283, 25706-25714.  
18959366 M.Łuczkowski, M.Stachura, V.Schirf, B.Demeler, L.Hemmingsen, and V.L.Pecoraro (2008).
Design of thiolate rich metal binding sites within a peptidic framework.
  Inorg Chem, 47, 10875-10888.  
18795800 T.Liu, X.Chen, Z.Ma, J.Shokes, L.Hemmingsen, R.A.Scott, and D.P.Giedroc (2008).
A Cu(I)-sensing ArsR family metal sensor protein with a relaxed metal selectivity profile.
  Biochemistry, 47, 10564-10575.  
17897948 J.Qin, H.L.Fu, J.Ye, K.Z.Bencze, T.L.Stemmler, D.E.Rawlings, and B.P.Rosen (2007).
Convergent evolution of a new arsenic binding site in the ArsR/SmtB family of metalloregulators.
  J Biol Chem, 282, 34346-34355.  
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.