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	Distinct Target Site of Lenacapavir in Immature HIV-1 and Concurrent Binding with the Maturation Inhibitor Bevirimat.
ジャーナル・号・ページ	J Am Chem Soc, Vol. 147, Issue 46, Page 42685-42700, Year 2025
掲載日	2025年11月19日
著者	Chunxiang Wu / Megan E Meuser / Juan S Rey / Hamed Meshkin / Rachel Yang / Swapnil C Devarkar / Christian Freniere / Jiong Shi / Christopher Aiken / Juan R Perilla / Yong Xiong /
PubMed 要旨	HIV-1 inhibitors, such as bevirimat (BVM) and lenacapavir (LEN), significantly reduce the production and maturation of infectious virions. However, their mechanisms remain unclear due to the absence ...HIV-1 inhibitors, such as bevirimat (BVM) and lenacapavir (LEN), significantly reduce the production and maturation of infectious virions. However, their mechanisms remain unclear due to the absence of high-resolution structures for BVM in complex with the immature Gag lattice and LEN's structural data being limited to the mature capsid. Utilizing perforated virus-like particles (VLPs) produced from mammalian cells, we determined in situ cryo-electron microscopy (cryo-EM) structures of HIV-1 with inhibitors. This allowed for the first structural determination of the native immature HIV-1 particle with BVM and LEN bound inside the VLPs at high resolutions. Our findings demonstrate that LEN not only binds the mature capsid but also targets the immature lattice in a distinct manner. The binding of LEN induces a conformational change in the capsid protein (CA) region and alters the architecture of the Gag lattice, which may affect the maturation process. In addition, a more accurate model of BVM engaging the Gag lattice is revealed, one that is independent of LEN binding. These insights expand our understanding of the inhibitory mechanisms of LEN and BVM on HIV-1 and provide valuable clues for the design of future inhibitors.
リンク	J Am Chem Soc / PubMed:41198571 / PubMed Central
手法	EM (単粒子)
解像度	2.1 - 3.18 Å
構造データ	45975 9cwv EMDB-45975, PDB-9cwv: Gag CA-SP1 immature lattice from intact enveloped virus-like particles 手法: EM (単粒子) / 解像度: 2.42 Å 46593 9d6c EMDB-46593, PDB-9d6c: Gag CA-SP1 immature lattice bound with Lenacapavir and Bevirimat from enveloped virus like particles 手法: EM (単粒子) / 解像度: 2.1 Å 46595 9d6e EMDB-46595, PDB-9d6e: Gag CA-SP1 immature lattice bound with Bevirimat from enveloped virus like particles 手法: EM (単粒子) / 解像度: 3.09 Å 46631 9d88 EMDB-46631, PDB-9d88: Gag CA-SP1 immature lattice from enveloped and perforated virus like particles 手法: EM (単粒子) / 解像度: 3.18 Å 47240 9dwd EMDB-47240, PDB-9dwd: Gag CA-SP1 immature lattice bound with Lenacapavir from enveloped virus like particles (T8I) 手法: EM (単粒子) / 解像度: 3.13 Å 47475 9e39 EMDB-47475, PDB-9e39: Gag CA-SP1 (T8I) immature lattice bound with Bevirimat from enveloped virus like particles 手法: EM (単粒子) / 解像度: 2.71 Å 71417 9p9l EMDB-71417, PDB-9p9l: Gag CA-SP1 immature lattice bound with Lenacapavir from enveloped virus like particles 手法: EM (単粒子) / 解像度: 2.28 Å 71418 9p9m EMDB-71418, PDB-9p9m: CA-SP1 immature lattice assembled in vitro with inhibitor lenacapavir (dialyzed to 50nM) 手法: EM (単粒子) / 解像度: 2.93 Å
化合物	ChemComp-IHP: INOSITOL HEXAKISPHOSPHATE ChemComp-HOH: WATER ChemComp-QNG: N-[(1S)-1-(3-{4-chloro-3-[(methylsulfonyl)amino]-1-(2,2,2-trifluoroethyl)-1H-indazol-7-yl}-6-[3-methyl-3-(methylsulfonyl)but-1-yn-1-yl]pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl]-2-[(3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl]acetamide / 薬剤, 抗レトロウイルス剤YM ChemComp-2I4*: 3alpha-[(3-carboxy-3-methylbutanoyl)oxy]-8alpha,9beta,10alpha,13alpha,17alpha,19beta-lup-20(29)-en-28-oic acid
由来	human immunodeficiency virus type 1 group m subtype b (isolate hxb2) (ヒト免疫不全ウイルス) human immunodeficiency virus type 1 (new york-5 isolate) (ヒト免疫不全ウイルス) human immunodeficiency virus type 1 (hbx2 isolate) (ヒト免疫不全ウイルス)
キーワード	VIRUS LIKE PARTICLE / Gag / CA-SP1 / HIV-1 / Inhibitor / virion assembly / VIRAL PROTEIN