4MDB

Structure of Mos1 transposase catalytic domain and Raltegravir with Mg

4MDB の概要

• エントリーDOI: 10.2210/pdb4mdb/pdb
• 関連するPDBエントリー: 2F7T 3HOS 3HOT 4MDA
• 分子名称: Mariner Mos1 transposase, N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(1-methyl-1-{[(5-methyl-1,3,4-oxadiazol-2-yl)carbonyl]amino}ethyl)-6-oxo-1,6-di hydropyrimidine-4-carboxamide, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: rnase-h fold, ddd motif, recombinase, dna transposition, dna integration, transposon dna, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Drosophila mauritiana (Fruit fly)
• 細胞内の位置: Nucleus (Probable): Q7JQ07
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27384.58

構造登録者

Richardson, J.M. (登録日: 2013-08-22, 公開日: 2014-01-22, 最終更新日: 2023-09-20)

主引用文献

Wolkowicz, U.M.,Morris, E.R.,Robson, M.,Trubitsyna, M.,Richardson, J.M.
Structural Basis of Mos1 Transposase Inhibition by the Anti-retroviral Drug Raltegravir.
Acs Chem.Biol., 9:743-751, 2014

PubMed Abstract: DNA 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 Mg(2+) or Mn(2+), 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 Mg(2+) or Mn(2+) 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.

PubMed: 24397848
DOI: 10.1021/cb400791u

実験手法

X-RAY DIFFRACTION (1.7 Å)