Journal article
Crystal structure of the HIV-1 integrase core domain in complex with sucrose reveals details of an allosteric inhibitory binding site
J Wielens, SJ Headey, D Jeevarajah, DI Rhodes, J Deadman, DK Chalmers, MJ Scanlon, MW Parker
FEBS Letters | Published : 2010
Abstract
HIV integrase (IN) is an essential enzyme in HIV replication and an important target for drug design. IN has been shown to interact with a number of cellular and viral proteins during the integration process. Disruption of these important interactions could provide a mechanism for allosteric inhibition of IN. We present the highest resolution crystal structure of the IN core domain to date. We also present a crystal structure of the IN core domain in complex with sucrose which is bound at the dimer interface in a region that has previously been reported to bind integrase inhibitors. Structured summary: MINT-7713125: IN (uniprotkb:. P04585) and IN (uniprotkb:. P04585) bind (MI:. 0407) by X-ra..
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Awarded by Australian Research Council Linkage
Awarded by Australian Research Council
Funding Acknowledgements
We thank Nick Vandegraaff for testing sucrose in the IN assay and Susanne Feil and Mike Gorman for support and advice. We also thank the BioCARS and GM/CA staff for their help at the Advanced Photon Source. This work was supported by the Australian Research Council Linkage project (LP0775192) and the Australian Synchrotron Research Program, which was funded by the Commonwealth of Australia under the Major National Research Facilities Program. Use of the Advanced Photon Source was supported by the U.S. DOE, Basic Energy Sciences and Office of Energy Research. M. W. P. is an ARC Federation Fellow and National Health and Medical Research Council Honorary Fellow.