Avian Sarcoma Virus Integrase with Other Molecules & Cations

 Home Page National Cancer Institute Macromolecular Crystallography Laboratory Retroviral Integrase Project NCI-Frederick MCL - Protein Structure Section
Structures determined by the Macromolecular Crystallography Laboratory, Protein Structure Section at the NCI-Frederick campus. Work performed in collaboration with the Skalka Laboratory in the Institute for Cancer Research, Fox Chase Cancer Center.




HEPES buffer electron density map
This image shows a molecule we never expected to see. When solving the first ASV IN structure, we saw something that did not look like a water molecule (the two separate red spheres). We had hoped it was a nucleotide, one of the building blocks of DNA, but it turned out to be a molecule of HEPES buffer, shown below. We still hope to solve the structure of DNA bound to an IN. In the meantime, the location of this bound HEPES and other, more direct evidence give us ideas about where to look for DNA bound to IN.





Bound molecules:
HEPES, citrate.






Nucleotide, not found.
(But still trying!)







This is one view of the surface of a dimer of the ASV IN catalytic core domain. The middle of the image shows the interface region between two monomers. The blue areas show the locations of positively charged amino acid residues, which would attract negatively charged DNA (or HEPES buffer). The red areas show negatively charged amino acid residues, which hold the catalytically activating metal cations (black dot) with associated water molecules (white dots). INs have many more positively charged residues on the surface than an "average" protein, similar to other DNA-binding proteins.




In addition to binding different buffer or inhibitor molecules, ASV IN also binds zinc cations away from the active site. This zinc-binding location may be structurally important. The zinc bound here may stabilize the IN structure.


Click here for more information about the interaction between ASV IN and essential cations or other cations and ASV IN.

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If you have questions or comments about the Integrase Project web site,
contact: Jerry N. Alexandratos at alexandr@ncifcrf.gov.