| 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. |
Crystals and structures of the
avian sarcoma virus integrase catalytic core domain
(monomer, left, and crystallographic dimer, right)
*Images courtesy Dr. Grzegorz Bujacz, Technical University of Lódz,
Poland,
former member of the Laboratory.
The Catalytic Core Domains of Integrases
Active Site of Avian Sarcoma Virus Integrase| The IN core domain contains the active site and performs theintegrationreaction. Along with the N- and C-termini, the core domain holdsthe DNAsubstrate. |
Comparison of ASV and HIV-1 Integrases
Integrase Flexible Loop.
Secondary Structure of Integrases.| ASV is related to HIV, since both are retroviruses. Their IN proteins are structurally related. Both have a flexible loop, which is believed to help properly bind, line up, and bend DNA in order to carry out the integration reaction. |
Essential Cations Bound by Avian Sarcoma Virus Integrase
More Cations Bound by Avian Sarcoma Virus Integrase| Like many enzymes, INs require metal cation cofactors for catalytic activity. The ASV IN 3D structure is the first IN crystal structure to show the location of these required cations. It is not yet known which specific metal cation is responsible for IN activity in a virally infected cell. |
Avian Sarcoma Virus Integrase with Other Molecules & Cations| Other molecules from our solutions also bind to ASV IN. |
| INs are structurally related not only to each other, but also to other proteins that bind DNA. |
Inhibitor Bound to Avian Sarcoma Virus Integrase
Interaction of Integrase Flexible Loop with Bound Y-3 Inhibitor| We collaborate with groups searching for inhibitors of HIV. This is the first crystal structure of an HIV-1 IN inhibitor bound to an IN molecule. With this knowledge of the structural interactions between IN and inhibitors, we hope that drug design groups will be able to produce better IN inhibitors, eventually leading to novel antiviral drugs. |
Integrase Structure Articles Published by the MCL
Integrase Crystal Structures Solved by the MCL
Links to Other Laboratories and Useful Sites
