Projects per year
DNA transposases catalyse the movement of transposons around genomes by a cut-and-paste mechanism related to retroviral integration. Transposases and retroviral integrases share a common RNaseH-like domain with a catalytic DDE/D triad that coordinates the divalent cations required for DNA cleavage and integration. The anti-retroviral drugs Raltegravir and Elvitegravir inhibit integrases by displacing viral DNA ends from the catalytic metal ions. We demonstrate that Raltegravir, but not Elvitegravir, binds to Mos1 transposase in the presence of Mg2+ or Mn2+, without the requirement for transposon DNA, and inhibits transposon cleavage and DNA integration in biochemical assays. Crystal structures at 1.7 Å resolution show Raltegravir, in common with integrases, coordinating two Mg2+ or Mn2+ ions in the Mos1 active site. However, in the absence of transposon ends, the drug adopts an unusual, compact binding mode distinct from that observed in the active site of the prototype foamy virus integrase.
|Journal||Acs chemical biology|
|Publication status||Published - 7 Jan 2014|
FingerprintDive into the research topics of 'The structural basis of Mos1 transposase inhibition by the anti-retroviral drug Raltegravir'. Together they form a unique fingerprint.
- 2 Finished
Molecular basis and manipulation of mariner/Tc1 transposon DNA integration
27/04/12 → 26/04/15
Molecular mechanisms of eukaryotic transpostion
1/10/08 → 31/12/13