PDBsum entry 3c3w

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Transcription PDB id
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Protein chains
211 a.a. *
Waters ×91
* Residue conservation analysis
PDB id:
Name: Transcription
Title: Crystal structure of the mycobacterium tuberculosis hypoxic regulator dosr
Structure: Two component transcriptional regulatory protein chain: a, b. Synonym: probably luxr/uhpa-family, devr, DNA-binding respo regulator, luxr family. Engineered: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: devr. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.20Å     R-factor:   0.189     R-free:   0.249
Authors: G.Wisedchaisri,M.Wu,D.R.Sherman,W.G.J.Hol
Key ref:
G.Wisedchaisri et al. (2008). Crystal structures of the response regulator DosR from Mycobacterium tuberculosis suggest a helix rearrangement mechanism for phosphorylation activation. J Mol Biol, 378, 227-242. PubMed id: 18353359 DOI: 10.1016/j.jmb.2008.02.029
28-Jan-08     Release date:   22-Apr-08    
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Protein chains
P9WMF9  (DEVR_MYCTU) -  Transcriptional regulatory protein DevR (DosR)
217 a.a.
211 a.a.
Key:    Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     host cell cytoplasmic vesicle   7 terms 
  Biological process     dormancy process   9 terms 
  Biochemical function     DNA binding     2 terms  


DOI no: 10.1016/j.jmb.2008.02.029 J Mol Biol 378:227-242 (2008)
PubMed id: 18353359  
Crystal structures of the response regulator DosR from Mycobacterium tuberculosis suggest a helix rearrangement mechanism for phosphorylation activation.
G.Wisedchaisri, M.Wu, D.R.Sherman, W.G.Hol.
The response regulator DosR is essential for promoting long-term survival of Mycobacterium tuberculosis under low oxygen conditions in a dormant state and may be responsible for latent tuberculosis in one-third of the world's population. Here, we report crystal structures of full-length unphosphorylated DosR at 2.2 A resolution and its C-terminal DNA-binding domain at 1.7 A resolution. The full-length DosR structure reveals several features never seen before in other response regulators. The N-terminal domain of the full-length DosR structure has an unexpected (beta alpha)(4) topology instead of the canonical (beta alpha)(5) fold observed in other response regulators. The linker region adopts a unique conformation that contains two helices forming a four-helix bundle with two helices from another subunit, resulting in dimer formation. The C-terminal domain in the full-length DosR structure displays a novel location of helix alpha 10, which allows Gln199 to interact with the catalytic Asp54 residue of the N-terminal domain. In contrast, the structure of the DosR C-terminal domain alone displays a remarkable unstructured conformation for helix alpha 10 residues, different from the well-defined helical conformations in all other known structures, indicating considerable flexibility within the C-terminal domain. Our structures suggest a mode of DosR activation by phosphorylation via a helix rearrangement mechanism.
  Selected figure(s)  
Figure 3.
Fig. 3. The DosR phosphorylation site. (a) The side chains of D8, D9, D54 (highlighted in yellow), T82 and D87 in the N-terminal domain (magenta), Y101 and K104 in the linker (blue), Q199 and E206 in the C-terminal domain (green) are shown as stick models. Y101 is vert, similar 12 Å away from T82. The D54–Q199 and D87–E206 hydrogen bonds contribute to contacts between helix α10 and the N-terminal domain. The latter hydrogen bonds require protonation of at lease one of the carboxylates. (b) A stereo view of the phosphorylation site. The σ[A]-weighted 2F[obs]–F[calc] electron density map of the phosphorylation site D54, contoured at the 1σ level is shown including neighboring residues.
Figure 4.
Fig. 4. The crystal structures of the DosR C-terminal domain. (a) The DosR^C dimer structure from crystal form II (DosR^C-II). Subunit A is shown in cyan and subunit B is shown in blue. The α10 helix is “melted” into a coiled coil, and the C-terminal tail after Gln199 is disordered.
  The above figures are reprinted from an Open Access publication published by Elsevier: J Mol Biol (2008, 378, 227-242) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21304599 U.S.Gautam, S.Chauhan, and J.S.Tyagi (2011).
Determinants outside the DevR C-terminal domain are essential for cooperativity and robust activation of dormancy genes in Mycobacterium tuberculosis.
  PLoS One, 6, e16500.  
20211578 R.B.Bourret (2010).
Receiver domain structure and function in response regulator proteins.
  Curr Opin Microbiol, 13, 142-149.  
20080056 R.Gao, and A.M.Stock (2010).
Molecular strategies for phosphorylation-mediated regulation of response regulator activity.
  Curr Opin Microbiol, 13, 160-167.  
18801459 D.J.Murphy, and J.R.Brown (2008).
Novel drug target strategies against Mycobacterium tuberculosis.
  Curr Opin Microbiol, 11, 422-427.  
  19052358 R.Schnell, D.Agren, and G.Schneider (2008).
1.9 A structure of the signal receiver domain of the putative response regulator NarL from Mycobacterium tuberculosis.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 1096-1100.
PDB code: 3eul
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