School of Biological Sciences

BIOL401: DNA, DNA-protein, DNA-drug and topoisomerase structures

Dr Andy Bates

These pages allow you to look at and manipulate the same structures as I was using in the BIOL401 lectures

You should see the DNA structures below in the table. If you do not, then your browser is not set up to use the Chime Plugin, which is used to display the coordinates of the structure. University W2KS machines should work without any problem. For further information about Chime, go to MDL, or the RasMol Home Page.

First, for best results, make sure the window of your browser fills the whole of your monitor, then click on the title of each structure to reveal the full page:

DNA, DNA complexes and topoisomerases

Below the DNA structures are links to DNA-drug, and DNA-protein complex and topoisomerase structures, with a brief dscription of the contents

Before you look at some real structures, you might like to look at a short tutorial: Why is DNA a helix?

It might also be useful to check out the following description of How to use Chime

Offprints of articles for this portion of the module are available from the Library Desk or, more conveniently, from the links below:

Kool, E. (2001). Hydrogen bonding, base stacking and steric effects in DNA replication. Annu. Rev. Biophys. Biomol. Struct. 30, 1-22.
You don't need to look at all of this - just pages 2-3, 5-7 and 10-12 about H-bonding and stacking will be quite sufficient

Morales, J. and Kool, E. (1998). Efficient replication between non-hydrogen-bonded nucleoside shape analogs. Nature Struct. Biol. 5, 950-954.
This is not available online, but should be in the library as a reprint.

Matray, T. and Kool, E. (1999). A specific partner for abasic damage in DNA. Nature 399, 704-708.

Ng, H.-L., Kopka, M. and Dickerson, R. (2000). The structure of a stable intermediate in the A-B DNA helix transition. Proc. Natl. Acad. Sci. USA 97, 2035-2039.

Dickerson, R. (1998). DNA bending: the prevalence of kinkiness and the virtues of normality. Nucleic Acids Res. 26 1906-1926.

Richmond, T. and Davey, C. (2003). The structure of DNA in the nucleosome core Nature 423, 145-150.

Powerpoint files:

DNA conformation

DNA-protein complexes

The following are pages devoted to the individual DNA-protein complex structures used in the lectures:

Ethidium bromide complex	The ethidium bromide molecule is shown bound between two base pairs of RNA; no structures with DNA exist, although we assume the basic idea is similar. The much reduced twisting between the base pairs is apparent
Netropsin-DNA complex	The minor groove-binding molecule, netropsin, is shown bound to a double-stranded DNA fragment.
434 Repressor-Operator complex	A 'simple' helix-turn-helix protein complexed with DNA, including a look at amino acid-base interactions in the major groove.
CRP/CAP complex	The complex of cAMP receptor protein with its DNA site, showing the residues involved in the bending of the DNA around the protein, and the distortion of the DNA.
Engrailed Homeodomain complex	A eukaryotic helix-turn-helix protein complex, showing additional interactions with base edges in the minor groove.
Single Zinc finger	The structure of a single zinc finger, showing the zinc coordination, the hydrophobic core and the position of the base-interacting residues.
Zif 268 complex	The complex of the DNA-binding domain of the Zif268 mouse transcription factor, which contains three zinc fingers, each contacting a triplet of base pairs.
Glucocorticoid receptor complex	The DNA-binding dimer of glucocorticoid receptor, model for the steroid hormone receptor family of trancription factors - each monomer contains two modified Zinc finger structures.
TBP-TATA box complex	The interaction of the TBP protein with a typical TATA box sequence, showing the huge distortion of the DNA and the binding of the protein on top of the minor groove.
DNase I DNA complex	A structure showing the bridging and opening out of the minor groove by DNase I.
Nucleosome structure	Full atomic resolution structure of the nucleosome.

DNA Topology-related structures

You may find it helpful to look at a recently published online article on topoisomerases from the Encyclopedia of Life Sciences - also search for 'Supercoiling" to find more:

Bates, A.D. (2001) Topoisomerases. in Encyclopedia of Life Sciences, Nature Publishing Group, London, www.els.net.

You need to search for 'Topoisomerases' from the front page.

You will only be able to access the article from a University computer, because the University is paying a licence fee.

Powerpoint files:

DNA topology

DNA topoisomerases

Topoisomerases in vivo

Structures:

E. coli topoisomerase I fragment	The structure of a 67 kDa fragment of the type IA topoisomerase. This fragment will cleave DNA, but not carry out the whole reaction. The active-site tyrosine is highlighted at the entrance to the internal cavity of the enzyme.
Human topoisomerase I-DNA covalent complex	The structure of the phosphotyrosine intermediate of the typeIB topoisomerase I enzyme is shown. The absence of a cavity, and the lack of distortion of the DNA makes it likely that the enzyme works by a simple rotation mechanism.
DNA gyrase ATPase domain	The dimeric structure of the 43 kDa ATPase domain of DNA gyrase is shown. The dimer forms permanently in the presence of a non-hydrolysable ATP analogue, 5´-adenylyl-beta,gamma-imiodiphosphate
DNA gyrase breakage-reunion domain	The dimeric structure of the N-terminal portion of the GyrA protein is shown, with the active site tyrosines highlighted. The G segment of DNA is believed to lie in the broove at the top of the molecule above the tyrosines.

I would be very grateful to receive any feedback from the use of these pages, particularly from BIOL401 students. If you do have a look at the pages, please drop me an Email, and let me know what you think.