1UNJ

Crystal structure of a 7-Aminoactinomycin D complex with non-complementary DNA

Summary for 1UNJ

• Entry DOI: 10.2210/pdb1unj/pdb
• Related: 173D 1A7Y 1A7Z 1DSC 1DSD 1FJA 1I3W 1L1V 1MNV 1OVF 1QFI 1UNM 209D 2D55 316D
• Related PRD ID: PRD_000010
• Descriptor: 5'-D(*TP*TP*AP*GP*BRU*TP)-3', 7-AMINO-ACTINOMYCIN D (3 entities in total)
• Functional Keywords: actinomycin d, actinomycin, antibiotic, anti cancer, antitumor, chromophore, depsipeptide, dna-antibiotic complex, fluorescent agent, hoogsten base-pair, dna/antibiotic
• Biological source: synthetic construct; More
• Total number of polymer chains: 24
• Total formula weight: 40517.22

Authors

Alexopoulos, E.C.,Klement, R.,Jares-Erijman, E.A.,Uson, I.,Jovin, T.M.,Sheldrick, G.M. (deposition date: 2003-09-10, release date: 2004-12-16, Last modification date: 2024-10-16)

Primary citation

Alexopoulos, E.C.,Jares-Erijman, E.A.,Jovin, T.M.,Klement, R.,Machinek, R.,Sheldrick, G.M.,Uson, I.
Crystal and Solution Structures of 7-Amino-Actinomycin D Complexes with D(Ttagbrut), D(Ttagtt) and D(Tttagttt)
Acta Crystallogr.,Sect.D, 61:407-, 2005

PubMed 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.

PubMed: 15805595
DOI: 10.1107/S090744490500082X

Experimental method

X-RAY DIFFRACTION (2.5 Å)