EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Sliding of HIV-1 reverse transcriptase over DNA creates a transient P pocket - targeting P-pocket by fragment screening.
ジャーナル・号・ページ	Nat Commun, Vol. 12, Issue 1, Page 7127, Year 2021
掲載日	2021年12月8日
著者	Abhimanyu K Singh / Sergio E Martinez / Weijie Gu / Hoai Nguyen / Dominique Schols / Piet Herdewijn / Steven De Jonghe / Kalyan Das /
PubMed 要旨	HIV-1 reverse transcriptase (RT) slides over an RNA/DNA or dsDNA substrate while copying the viral RNA to a proviral DNA. We report a crystal structure of RT/dsDNA complex in which RT overstepped the ...HIV-1 reverse transcriptase (RT) slides over an RNA/DNA or dsDNA substrate while copying the viral RNA to a proviral DNA. We report a crystal structure of RT/dsDNA complex in which RT overstepped the primer 3'-end of a dsDNA substrate and created a transient P-pocket at the priming site. We performed a high-throughput screening of 300 drug-like fragments by X-ray crystallography that identifies two leads that bind the P-pocket, which is composed of structural elements from polymerase active site, primer grip, and template-primer that are resilient to drug-resistance mutations. Analogs of a fragment were synthesized, two of which show noticeable RT inhibition. An engineered RT/DNA aptamer complex could trap the transient P-pocket in solution, and structures of the RT/DNA complex were determined in the presence of an inhibitory fragment. A synthesized analog bound at P-pocket is further analyzed by single-particle cryo-EM. Identification of the P-pocket within HIV RT and the developed structure-based platform provide an opportunity for the design new types of polymerase inhibitors.
リンク	Nat Commun / PubMed:34880240 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	2.85 - 3.58 Å
構造データ	13139 7ozw EMDB-13139, PDB-7ozw: Cryo-EM structure of HIV-1 reverse transcriptase with a DNA aptamer in complex with fragment 166 at the transient P-pocket 手法: EM (単粒子) / 解像度: 3.38 Å 13156 7p15 EMDB-13156, PDB-7p15: Cryo-EM structure of HIV-1 reverse transcriptase with a DNA aptamer in complex with fragment F04 at the transient P-pocket 手法: EM (単粒子) / 解像度: 3.58 Å PDB-7oxq: Crystal structure of HIV-1 reverse transcriptase with a double stranded DNA in complex with fragment 048 at the transient P-pocket. 手法: X-RAY DIFFRACTION / 解像度: 3.3 Å PDB-7oz2: Crystal structure of HIV-1 reverse transcriptase with a double stranded DNA showing a transient P-pocket 手法: X-RAY DIFFRACTION / 解像度: 2.85 Å PDB-7oz5: Crystal structure of HIV-1 reverse transcriptase with a double stranded DNA in complex with fragment 166 at the transient P-pocket. 手法: X-RAY DIFFRACTION / 解像度: 3.37 Å
化合物	ChemComp-CD: Unknown entry ChemComp-2NU: 2-(4-bromanylpyrazol-1-yl)-~{N}-cyclopropyl-~{N}-methyl-ethanamide ChemComp-SO4: SULFATE ION / 硫酸ジアニオン ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-HOH: WATER ChemComp-3IR: (1~{R},2~{R})-2-phenyl-~{N}-(1,3-thiazol-2-yl)cyclopropane-1-carboxamide ChemComp-4OI: (1~{R},2~{R})-~{N}-(1~{H}-pyrazol-4-yl)-2-pyridin-3-yl-cyclopropane-1-carboxamide
由来	human immunodeficiency virus type 1 bh10 (ヒト免疫不全ウイルス) human immunodeficiency virus type 1 group m subtype b (isolate bh10) (ヒト免疫不全ウイルス) synthetic construct (人工物) homo sapiens (ヒト)
キーワード	TRANSFERASE / Reverse Transcriptase / RT-DNA complex / RT sliding / Transferase-DNA complex / P-1 complex / P51 / P66 / RT-aptamer complex