PDBsum entry 2alc

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protein metals links
DNA binding protein PDB id
Protein chain
65 a.a. *
_ZN ×2
* Residue conservation analysis
PDB id:
Name: DNA binding protein
Title: Ethanol regulon transcriptional activator DNA-binding domain from aspergillus nidulans
Structure: Protein (ethanol regulon transcriptional activator). Chain: a. Fragment: DNA-binding domain. Engineered: yes
Source: Emericella nidulans. Organism_taxid: 162425. Gene: alcr. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 1 models
Authors: R.Cerdan,B.Cahuzac,B.Felenbok,E.Guittet
Key ref:
R.Cerdan et al. (2000). NMR solution structure of AlcR (1-60) provides insight in the unusual DNA binding properties of this zinc binuclear cluster protein. J Mol Biol, 295, 729-736. PubMed id: 10656785 DOI: 10.1006/jmbi.1999.3417
20-Jan-99     Release date:   21-Jan-00    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P21228  (ALCR_EMENI) -  Regulatory protein alcR
821 a.a.
65 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     regulation of transcription, DNA-dependent   1 term 
  Biochemical function     sequence-specific DNA binding RNA polymerase II transcription factor activity     2 terms  


DOI no: 10.1006/jmbi.1999.3417 J Mol Biol 295:729-736 (2000)
PubMed id: 10656785  
NMR solution structure of AlcR (1-60) provides insight in the unusual DNA binding properties of this zinc binuclear cluster protein.
R.Cerdan, B.Cahuzac, B.Félenbok, E.Guittet.
The three-dimensional structure of the DNA-binding domain (residues 1-60) of the ethanol regulon transcription factor AlcR from Aspergillus nidulans has been solved by NMR. This domain belongs to the zinc binuclear cluster class. Although the core of the protein is similar to previously characterized structures, consisting of two helices organized around a Zn(2)Cys(6 )motif, the present structure presents important variations, among them the presence of two supplementary helices. This structure gives new insight into the understanding of the AlcR specificities in DNA binding such as longer consensus half-sites, in vitro monomeric binding but in vivo multiple repeat transcriptional activation, either in direct or inverse orientations. The presence of additional contacts of the protein with its DNA target can be predicted from a model proposed for the interaction with the consensus DNA target. The clustering of accessible negative charges on helix 2 delineates a possible interaction site for other determinants of the transcriptional machinery, responsible for the fine tuning of the selection of the AlcR cognate sites.
  Selected figure(s)  
Figure 2.
Figure 2. (a) Ribbon diagram of the lowest energy structure of AlcR DNA-binding domain (9-60). The four a-helices correspond to residues 13 to 18, 28 to 34, 40 to 45 and 52 to 56. The side-chains of residues defining the hydrophobic core (see the text) are displayed in ball-and-stick representation. (b) Stereo view of the 17 calculated structures of AlcR(7-60). Backbone atoms are superimposed to the mean structure for residues 9 to 56. The two zinc atoms are represented as purple spheres. (c) Electrostatic plot of AlcR (residues 9-60). Basic charges are shown in blue while acidic charges are red. The principal solvent exposed side-chains are named. The residues likely involved in the DNA recognition (see the text) are boxed. A total number of 970 NOEs were identified on nuclear Overhauser enhancement spectroscopy (NOESY) and heteronuclear single quantum coherence (HSQC) spectra. A total of 32 CH[2] and four CH[3] groups were stereospecifically assigned. The restraints on phi, Greek angles were based on measurements of the vicinal coupling constants 3J[[HN-Ha]] obtained from a HNHA experiment [Vuister and Bax 1993]. In addition, 23 hydrogen bonds, identified in the preliminary structures and confirmed by amide proton exchange (see the text), were converted into 46 distance restraints: the distance interval between the hydrogen atom (donor heavy atom) and the acceptor atom was set to 1.8-2.5 Å(2.8-3.5 Å), respectively. The distance and angle contraints related to the zinc co-ordination were set to 3.16 Åfor the Zn-Zn distance, 2.34 Åfor the S-Zn distances, 109 ° for the S-Zn-S angles, 109 ° for the C^b-S-Zn angles and 70 ° for the Zn-S-Zn angles. All plots were generated using InsightII and Delphi (MSI Corp.).
Figure 4.
Figure 4. Model of the ALCR-DNA complex, built by superimposing a representative AlcR structure on the GAL4-DNA complex [Marmorstein et al 1992]. The DNA consensus half-site of GAL4 corresponds to the green base-pairs while the AlcR site extends over green and blue base-pairs.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 295, 729-736) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
15813742 M.Mathieu, I.Nikolaev, C.Scazzocchio, and B.Felenbok (2005).
Patterns of nucleosomal organization in the alc regulon of Aspergillus nidulans: roles of the AlcR transcriptional activator and the CreA global repressor.
  Mol Microbiol, 56, 535-548.  
12684370 I.Nikolaev, M.F.Cochet, and B.Felenbok (2003).
Nuclear import of zinc binuclear cluster proteins proceeds through multiple, overlapping transport pathways.
  Eukaryot Cell, 2, 209-221.  
12861007 J.H.Kim, J.Polish, and M.Johnston (2003).
Specificity and regulation of DNA binding by the yeast glucose transporter gene repressor Rgt1.
  Mol Cell Biol, 23, 5208-5216.  
11972793 D.Gómez, B.Cubero, G.Cecchetto, and C.Scazzocchio (2002).
PrnA, a Zn2Cys6 activator with a unique DNA recognition mode, requires inducer for in vivo binding.
  Mol Microbiol, 44, 585-597.  
11266598 G.Marie, L.Serani, O.Laprévote, B.Cahuzac, E.Guittet, and B.Felenbok (2001).
Differential chemical labeling of the AlcR DNA-binding domain from Aspergillas nidulans versus its complex with a 16-mer DNA target: identification of an essential tryptophan involved in the recognition and the interaction with the nucleic acid.
  Protein Sci, 10, 99.  
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