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Structure of Mos1 transposase catalytic domain and Raltegravir with MnStructure of Mos1 transposase catalytic domain and Raltegravir with Mn
Structural highlights
Publication Abstract from PubMedDNA transposases catalyze 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 A 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. Structural Basis of Mos1 Transposase Inhibition by the Anti-retroviral Drug Raltegravir.,Wolkowicz UM, Morris ER, Robson M, Trubitsyna M, Richardson JM ACS Chem Biol. 2014 Jan 10. PMID:24397848[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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