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PDBsum entry 1mnv
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protein dna_rna Protein-protein interface(s) links
DNA/antibiotic PDB id
1mnv

 

 

 

 

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Contents
Protein chains
11 a.a.
DNA/RNA
Waters ×65
PDB id:
1mnv
Name: DNA/antibiotic
Title: Actinomycin d binding to atgctgcat
Structure: 5'-d( Ap Tp Gp Cp Tp Gp Cp Ap T)-3'. Chain: a, b. Engineered: yes. Actinomycin d. Chain: c, d. Synonym: dactinomycin. Engineered: yes
Source: Synthetic: yes. Other_details: this sequence occurs naturally in humans. Streptomyces antibioticus. Organism_taxid: 1890
Biol. unit: Tetramer (from PQS)
Resolution:
2.60Å     R-factor:   0.233     R-free:   0.295
Authors: M.-H.Hou,H.Robinson,Y.-G.Gao,A.H.-J.Wang
Key ref: M.H.Hou et al. (2002). Crystal structure of actinomycin D bound to the CTG triplet repeat sequences linked to neurological diseases. Nucleic Acids Res, 30, 4910-4917. PubMed id: 12433994 DOI: 10.1093/nar/gkf619
Date:
06-Sep-02     Release date:   22-Nov-02    
PROCHECK
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 Headers
 References

Protein chains
No UniProt id for this chain
Struc: 11 a.a.
Key:    Secondary structure

DNA/RNA chains
  A-T-G-C-T-G-C-A-T 9 bases
  A-T-G-C-T-G-C-A-T 9 bases

 

 
DOI no: 10.1093/nar/gkf619 Nucleic Acids Res 30:4910-4917 (2002)
PubMed id: 12433994  
 
 
Crystal structure of actinomycin D bound to the CTG triplet repeat sequences linked to neurological diseases.
M.H.Hou, H.Robinson, Y.G.Gao, A.H.Wang.
 
  ABSTRACT  
 
The potent anticancer drug actinomycin D (ActD) acts by binding to DNA GpC sequences, thereby interfering with essential biological processes including replication, transcription and topoisomerase. Certain neurological diseases are correlated with expansion of (CTG)n trinucleotide sequences, which contain many contiguous GpC sites separated by a single base pair. In order to characterize the binding of ActD to CTG triplet repeat sequences, we carried out heat denaturation and CD analyses, which showed that adjacent GpC sequences flanking a T:T mismatch are preferred ActD-binding sites, and that ActD binding results in a conformational transition to A-type structure. The structural basis of the strong binding of ActD to neighboring GpC sites flanking a T:T mismatch was provided by the crystal structure of ActD bound to ATGCTGCAT, which contains a CTG triplet sequence. Binding of two ActD molecules to GCTGC causes a kink in the DNA helix. In addition, using a synthetic self-priming DNA model, 5'-(CAG)4(CTG)(16)-3', we observed that ActD can trap the cruciform or duplexes of (CTG)n and interfere with the expansion process of CTG triplet repeats as shown by gel electrophoretic expansion assay. Our results may provide the possible biological consequence of ActD bound to CTG triplet repeat sequences.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21324982 N.Vekshin (2011).
Melting of DNA-actinomycin clusters.
  J Biochem, 149, 601-607.  
21127174 S.Kayser, K.Döhner, J.Krauter, C.H.Köhne, H.A.Horst, G.Held, M.von Lilienfeld-Toal, S.Wilhelm, A.Kündgen, K.Götze, M.Rummel, D.Nachbaur, B.Schlegelberger, G.Göhring, D.Späth, C.Morlok, M.Zucknick, A.Ganser, H.Döhner, and R.F.Schlenk (2011).
The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML.
  Blood, 117, 2137-2145.  
19120688 G.Caprara, R.Zamponi, M.Melixetian, and K.Helin (2009).
Isolation and characterization of DUSP11, a novel p53 target gene.
  J Cell Mol Med, 13, 2158-2170.  
18712773 C.Y.Ho, C.H.Wong, and H.Y.Li (2008).
Perturbation of the chromosomal binding of RCC1, Mad2 and survivin causes spindle assembly defects and mitotic catastrophe.
  J Cell Biochem, 105, 835-846.  
16439138 M.A.Lewis, and E.C.Long (2006).
Fluorescent intercalator displacement analyses of DNA binding by the peptide-derived natural products netropsin, actinomycin, and bleomycin.
  Bioorg Med Chem, 14, 3481-3490.  
15805595 E.Alexopoulos, E.A.Jares-Erijman, T.M.Jovin, R.Klement, R.Machinek, G.M.Sheldrick, and I.Usón (2005).
Crystal and solution structures of 7-amino-actinomycin D complexes with d(TTAGBrUT), d(TTAGTT) and d(TTTAGTTT).
  Acta Crystallogr D Biol Crystallogr, 61, 407-415.
PDB codes: 1unj 1unm
15741187 M.H.Hou, and A.H.Wang (2005).
Mithramycin forms a stable dimeric complex by chelating with Fe(II): DNA-interacting characteristics, cellular permeation and cytotoxicity.
  Nucleic Acids Res, 33, 1352-1361.  
15556400 M.Egli (2004).
Nucleic acid crystallography: current progress.
  Curr Opin Chem Biol, 8, 580-591.  
15107489 M.H.Hou, H.Robinson, Y.G.Gao, and A.H.Wang (2004).
Crystal structure of the [Mg2+-(chromomycin A3)2]-d(TTGGCCAA)2 complex reveals GGCC binding specificity of the drug dimer chelated by a metal ion.
  Nucleic Acids Res, 32, 2214-2222.
PDB code: 1vaq
12736312 K.H.Chin, F.M.Chen, and S.H.Chou (2003).
Solution structure of the ActD-5'-CCGTT3GTGG-3' complex: drug interaction with tandem G.T mismatches and hairpin loop backbone.
  Nucleic Acids Res, 31, 2622-2629.
PDB code: 1ovf
12736295 S.H.Chou, K.H.Chin, and A.H.Wang (2003).
Unusual DNA duplex and hairpin motifs.
  Nucleic Acids Res, 31, 2461-2474.  
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 codes are shown on the right.

 

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