PDBsum entry 1zlk

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protein dna_rna Protein-protein interface(s) links
Transcription/DNA PDB id
Protein chains
65 a.a. *
* Residue conservation analysis
PDB id:
Name: Transcription/DNA
Title: Crystal structure of the mycobacterium tuberculosis hypoxic response regulator dosr c-terminal domain-DNA complex
Structure: 5'- d( Gp Gp Cp Cp Cp Gp Cp Gp Cp Tp Tp Tp Gp Gp Gp Gp Ap Cp Tp Ap Ap Ap Gp Tp Cp Cp Cp Tp Ap Ap Cp Cp Cp Tp Gp Gp Cp Cp A p Cp Gp Ap T)-3'. Chain: c. Engineered: yes. 5'- d( Cp Gp Tp Gp Gp Cp Cp Ap Gp Gp Gp Tp Tp Ap Gp Gp Gp Ap Cp Tp Tp Tp Ap Gp Tp Cp Cp Cp Cp Ap Ap Ap Gp Cp Gp Cp Gp Gp G
Source: Synthetic: yes. Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: dosr, devr, rv3133c. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Tetramer (from PQS)
3.10Å     R-factor:   0.272     R-free:   0.288
Authors: G.Wisedchaisri,M.Wu,A.E.Rice,D.M.Roberts,D.R.Sherman, W.G.J.Hol
Key ref:
G.Wisedchaisri et al. (2005). Structures of Mycobacterium tuberculosis DosR and DosR-DNA complex involved in gene activation during adaptation to hypoxic latency. J Mol Biol, 354, 630-641. PubMed id: 16246368 DOI: 10.1016/j.jmb.2005.09.048
06-May-05     Release date:   31-Jan-06    
Go to PROCHECK summary

Protein chains
P9WMF8  (DEVR_MYCTO) -  Transcriptional regulatory protein DevR (DosR)
217 a.a.
65 a.a.
Key:    Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     regulation of transcription, DNA-dependent   1 term 
  Biochemical function     DNA binding     2 terms  


DOI no: 10.1016/j.jmb.2005.09.048 J Mol Biol 354:630-641 (2005)
PubMed id: 16246368  
Structures of Mycobacterium tuberculosis DosR and DosR-DNA complex involved in gene activation during adaptation to hypoxic latency.
G.Wisedchaisri, M.Wu, A.E.Rice, D.M.Roberts, D.R.Sherman, W.G.Hol.
On encountering low oxygen conditions, DosR activates the transcription of 47 genes, promoting long-term survival of Mycobacterium tuberculosis in a non-replicating state. Here, we report the crystal structures of the DosR C-terminal domain and its complex with a consensus DNA sequence of the hypoxia-induced gene promoter. The DosR C-terminal domain contains four alpha-helices and forms tetramers consisting of two dimers with non-intersecting dyads. In the DNA-bound structure, each DosR C-terminal domain in a dimer places its DNA-binding helix deep into the major groove, causing two bends in the DNA. DosR makes numerous protein-DNA base contacts using only three amino acid residues per subunit: Lys179, Lys182, and Asn183. The DosR tetramer is unique among response regulators with known structures.
  Selected figure(s)  
Figure 2.
Figure 2. The DosRC dimers and tetramer. (a) The tetramer ABCD is made up of the AB and CD dimers related by the central 2[BC] 2-fold relating subunits B and C. Note that the 2-fold axes do not intersect. Subunits are colored with A yellow, B magenta, C gold, and D pink. (b) Stereo view of the a10 dimer interface between subunits A and B. Thr198, Val202, and Thr205 are the key contacting residues on helix a10. (c) Stereo view of residues making contacts at the a7/a8 tetramer interface between subunits B and C. For clarity, only Leu147, Arg155, Leu158, Leu207, and Lys208 of subunit B and Phe175 of subunit C are labeled. (d) Close-up view of the solvent-accessible surface of DosRC subunit B showing a hydrophobic pocket interacting with Phe175 of subunit C at the a7/a8 tetramer interface. The surface is colored by atom type: gray for carbon, red for oxygen, and blue for nitrogen.
Figure 3.
Figure 3. DosRC-DNA complex structure. (a) Stereo view of s[A]-weighted 2F[obs] -F[calc] electron density map contoured at the 1s level where Lys179, Lys182, and Asn183 interact with nucleotide bases. Due to the limited resolution and high anisotropy of the data, the side-chain densities are not as well defined as would have been possible with better diffracting crystals. Such crystals were not obtained in this case, however. (b) Structure of the DosRC-DNA complex. DosRC uses the a10 helices to form a functional dimer for DNA binding. Arg196, Thr198, Val202, and Thr205 are residues contributing to this dimerization interface. The DNA clearly has a bent conformation, as shown by its helical axis in gray. (c) Stereo view of the DosR tetramer-DNA complex. The a7/a8 dimer interface is formed between DosRC subunit B and its neighboring crystallographic symmetry-related subunit A' forming a tetramer ABA'B' similar to tetramer ABCD in the uncomplexed DosRC structure. (d) Contacts between DosRC dimer and the 20 bp consensus promoter of hypoxic response genes. Amino acid residues making DNA phosphate oxygen interactions are colored by subunit: yellow for subunit A and magenta for subunit B. Residues contacting nucleotide bases as well as the nucleotide bases interacting with the protein are colored blue for hydrogen bonds and red for van der Waals interactions. The backbone of the DNA is colored by DNA strand, cyan for strand I, and green for strand J. (e) Comparison of uncomplexed DosRC (white) and DNA-bound DosRC (green). The base-contacting residues Lys179, Lys182 and Asn183 are shown in stick model. A 5° rotation of the entire subunit B with respect to subunit A occurs upon binding to the DNA duplex. This decreases the distances between C^a atoms of the two Lys179 residues in the dimer by 1.5 Å, the two Lys182 residues by 1.0 Å, and the two Asn183 residues by 0.4 Å.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 354, 630-641) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20302877 C.A.Hobbs, B.G.Bobay, R.J.Thompson, M.Perego, and J.Cavanagh (2010).
NMR solution structure and DNA-binding model of the DNA-binding domain of competence protein A.
  J Mol Biol, 398, 248-263.
PDB code: 2krf
20080056 R.Gao, and A.M.Stock (2010).
Molecular strategies for phosphorylation-mediated regulation of response regulator activity.
  Curr Opin Microbiol, 13, 160-167.  
20520597 S.Boakes, A.N.Appleyard, J.Cortés, and M.J.Dawson (2010).
Organization of the biosynthetic genes encoding deoxyactagardine B (DAB), a new lantibiotic produced by Actinoplanes liguriae NCIMB41362.
  J Antibiot (Tokyo), 63, 351-358.  
21217812 S.Thao, C.S.Chen, H.Zhu, and J.C.Escalante-Semerena (2010).
Nε-lysine acetylation of a bacterial transcription factor inhibits Its DNA-binding activity.
  PLoS One, 5, e15123.  
19126546 R.K.Carroll, X.Liao, L.K.Morgan, E.M.Cicirelli, Y.Li, W.Sheng, X.Feng, and L.J.Kenney (2009).
Structural and Functional Analysis of the C-terminal DNA Binding Domain of the Salmonella typhimurium SPI-2 Response Regulator SsrB.
  J Biol Chem, 284, 12008-12019.  
19648251 S.Chauhan, and J.S.Tyagi (2009).
Powerful induction of divergent tgs1-Rv3131 genes in Mycobacterium tuberculosis is mediated by DevR interaction with a high-affinity site and an adjacent cryptic low-affinity site.
  J Bacteriol, 191, 6075-6081.  
19388905 T.R.Rustad, A.M.Sherrid, K.J.Minch, and D.R.Sherman (2009).
Hypoxia: a window into Mycobacterium tuberculosis latency.
  Cell Microbiol, 11, 1151-1159.  
18353359 G.Wisedchaisri, M.Wu, D.R.Sherman, and W.G.Hol (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.
PDB codes: 3c3w 3c57
18391009 H.M.Vasudeva-Rao, and K.A.McDonough (2008).
Expression of the Mycobacterium tuberculosis acr-coregulated genes from the DevR (DosR) regulon is controlled by multiple levels of regulation.
  Infect Immun, 76, 2478-2489.  
20477209 H.Tomioka, Y.Tatano, K.Yasumoto, and T.Shimizu (2008).
Recent advances in antituberculous drug development and novel drug targets.
  Expert Rev Respir Med, 2, 455-471.  
18359816 S.Chauhan, and J.S.Tyagi (2008).
Cooperative binding of phosphorylated DevR to upstream sites is necessary and sufficient for activation of the Rv3134c-devRS operon in Mycobacterium tuberculosis: implication in the induction of DevR target genes.
  J Bacteriol, 190, 4301-4312.  
18502855 S.Chauhan, and J.S.Tyagi (2008).
Interaction of DevR with multiple binding sites synergistically activates divergent transcription of narK2-Rv1738 genes in Mycobacterium tuberculosis.
  J Bacteriol, 190, 5394-5403.  
17655757 D.J.Murphy, and J.R.Brown (2007).
Identification of gene targets against dormant phase Mycobacterium tuberculosis infections.
  BMC Infect Dis, 7, 84.  
17991041 G.van Keulen, J.Alderson, J.White, and R.G.Sawers (2007).
The obligate aerobic actinomycete Streptomyces coelicolor A3(2) survives extended periods of anaerobic stress.
  Environ Microbiol, 9, 3143-3149.  
17283091 L.Woolhiser, M.H.Tamayo, B.Wang, V.Gruppo, J.T.Belisle, A.J.Lenaerts, R.J.Basaraba, and I.M.Orme (2007).
In vivo adaptation of the Wayne model of latent tuberculosis.
  Infect Immun, 75, 2621-2625.  
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 code is shown on the right.