English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Crystal and solution structures of 7-amino-actinomycin D complexes with d(TTAGBrUT), d(TTAGTT) and d(TTTAGTTT)

Alexopoulos, E., Jares-Erijman, E. A., Jovin, T. M., Klement, R., Sheldrick, G. M., & Uson, I. (2005). Crystal and solution structures of 7-amino-actinomycin D complexes with d(TTAGBrUT), d(TTAGTT) and d(TTTAGTTT). Acta Crystallographica D, 61: doi:10.1107/S090744490500082X, pp. 407-415. Retrieved from http://journals.iucr.org/d/issues/2005/04/00/fw5019/index.html.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0012-E9EB-B Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-DB12-1
Genre: Journal Article

Files

show Files
hide Files
:
214028.pdf (Publisher version), 0B
 
File Permalink:
-
Name:
214028.pdf
Description:
-
Visibility:
Restricted (Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute), Göttingen; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Alexopoulos, E., Author
Jares-Erijman, E. A.1, Author              
Jovin, T. M.1, Author              
Klement, R.2, Author              
Sheldrick, G. M., Author
Uson, I., Author
Affiliations:
1Department of Molecular Biology, MPI for biophysical chemistry, Max Planck Society, ou_578628              
2Emeritus Group Laboratory of Cellular Dynamics, MPI for biophysical chemistry, Max Planck Society, ou_578629              

Content

show
hide
Free keywords: Actinomycin D; single-stranded DNA; MAD phasing; NMR; molecular dynamics; molecular modeling
 Abstract: Synopsis: In the crystal, actinomycin D intercalates between G-T wobble pairs of DNA involving the sequence d(TTAGTT); in solution, the dominant binding is between guanine and actinomycin. 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 modeling. The crystal structures of the complex with 5'-TTAG[Br5U]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, 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 symmetry related molecule. The chromophore of the second actinomycin intercalates between 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 for determining 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.

Details

show
hide
Language(s):
 Dates: 2004-04-042005-03
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Acta Crystallographica D
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 61 Sequence Number: doi:10.1107/S090744490500082X Start / End Page: 407 - 415 Identifier: -