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PDBsum entry 1unj

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protein dna_rna links
DNA/antibiotic PDB id
1unj
Jmol
Contents
Protein chains
(+ 2 more) 11 a.a.
DNA/RNA
Waters ×14
PDB id:
1unj
Name: DNA/antibiotic
Title: Crystal structure of a 7-aminoactinomycin d complex with non-complementary DNA
Structure: 5'-d( Tp Tp Ap Gp Bru Tp)-3'. Chain: a, b, c, d, g, h, i, j, m, n, o, p, s, t, u, v. 7-amino-actinomycin d. Chain: e, f, k, l, q, r, w, x. Synonym: dactinomycin
Source: Synthetic: yes. Streptomyces antibioticus. Organism_taxid: 1890
Biol. unit: Monomer (from PDB file)
Resolution:
2.50Å     R-factor:   0.276     R-free:   0.316
Authors: E.C.Alexopoulos,R.Klement,E.A.Jares-Erijman,I.Uson,T.M.Jovin G.M.Sheldrick
Key ref:
E.Alexopoulos et al. (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. PubMed id: 15805595 DOI: 10.1107/S090744490500082X
Date:
10-Sep-03     Release date:   16-Dec-04    
PROCHECK
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 Headers
 References

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

 

 
DOI no: 10.1107/S090744490500082X Acta Crystallogr D Biol Crystallogr 61:407-415 (2005)
PubMed id: 15805595  
 
 
Crystal and solution structures of 7-amino-actinomycin D complexes with d(TTAGBrUT), d(TTAGTT) and d(TTTAGTTT).
E.Alexopoulos, E.A.Jares-Erijman, T.M.Jovin, R.Klement, R.Machinek, G.M.Sheldrick, I.Usón.
 
  ABSTRACT  
 
The formation of the complex of 7-amino-actinomycin D with potentially single-stranded DNA has been studied by X-ray crystallography in the solid state, by NMR in solution and by molecular modelling. The crystal structures of the complex with 5'-TTAG[Br(5)U]T-3' provide interesting examples of MAD phasing in which the dispersive component of the MAD signal was almost certainly enhanced by radiation damage. The trigonal and orthorhombic crystal modifications both contain antibiotic molecules and DNA strands in the form of a 2:4 complex: in the orthorhombic form there is one such complex in the asymmetric unit, while in the trigonal structure there are four. In both structures the phenoxazone ring of the first drug intercalates between a BrU-G (analogous to T-G) wobble pair and a G-T pair where the T is part of a symmetry-related molecule. The chromophore of the second actinomycin intercalates between the BrU-G and G-BrU wobble pairs of the partially paired third and fourth strands. The base stacking also involves (A*T)*T triplets and Watson-Crick A-T pairs and leads to similar complex three-dimensional networks in both structures, with looping-out of unpaired bases. Although the available NOE constraints of a solution containing the antibiotic and d(TTTAGTTT) strands in the ratio 1:1 are insufficient to determine the structure of the complex from the NMR data alone, they are consistent with the intercalation geometry observed in the crystal structure. Molecular-dynamics (MD) trajectories starting from the 1:2 complexes observed in the crystal showed that although the thymines flanking the d(AGT) core are rather flexible and the G-T pairing is not permanently preserved, both strands remain bound to the actinomycin by strong interactions between it and the guanines between which it is sandwiched. Similar strong binding (hemi-intercalation) of the actinomycin to a single guanine was observed in the MD trajectories of a 1:1 complex. The dominant interaction is between the antibiotic and guanine, but the complexes are stabilized further by promiscuous base-pairing.
 
  Selected figure(s)  
 
Figure 2.
Figure 2 (a) The mismatched wobble base pair G304-BrU105 with hydrogen bonding between the N1 and the O6 of the guanine with the O2 and the N3 of the bromouracil, respectively; (b) the mismatched base pair G104-T206* showing similar interactions; (c) in a T*A*T triplet, A403 makes Watson-Crick interactions with T102* and Hoogsten interactions with T101*; (d) [174][pi] -stacking of BrU305 to the phenoxazone ring of actinomycin molecule 1 (* indicates symmetry equivalent).
Figure 4.
Figure 4 Variation of NOE distances during the MD simulation (model 1): (a) H [alpha] (DPR4) with the H2'1(T17) (weak), (b) methyl group of DTH4 and the H1' of G16 (strong), (c) average distance between the AMD chromophore and the base G16, (d) average distance between the AMD chromophore and the base T17. G16 remains stacked on the chromophore over the entire range of the simulation, whereas T17 at first strongly fluctuates and then locks in into a stacked position.
 
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2005, 61, 407-415) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19348506 J.S.Hudson, S.C.Brooks, and D.E.Graves (2009).
Interactions of actinomycin D with human telomeric G-quadruplex DNA.
  Biochemistry, 48, 4440-4447.  
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