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	A Strain-Specific Inhibitor of Receptor-Bound HIV-1 Targets a Pocket near the Fusion Peptide.
ジャーナル・号・ページ	Cell Rep, Vol. 33, Issue 8, Page 108428, Year 2020
掲載日	2020年11月24日
著者	Gabriel Ozorowski / Jonathan L Torres / Diogo Santos-Martins / Stefano Forli / Andrew B Ward /
PubMed 要旨	Disruption of viral fusion represents a viable, albeit under-explored, target for HIV therapeutics. Here, while studying the receptor-bound envelope glycoprotein conformation by cryoelectron ...Disruption of viral fusion represents a viable, albeit under-explored, target for HIV therapeutics. Here, while studying the receptor-bound envelope glycoprotein conformation by cryoelectron microscopy (cryo-EM), we identify a pocket near the base of the trimer containing a bound detergent molecule and perform in silico drug screening by using a library of drug-like and commercially available molecules. After down-selection, we solve cryo-EM structures that validate the binding of two small molecule hits in very similar manners to the predicted binding poses, including interactions with aromatic residues within the fusion peptide. One of the molecules demonstrates low micromolar inhibition of the autologous virus by using a very rare phenylalanine in the fusion peptide and stabilizing the surrounding region. This work demonstrates that small molecules can target the fusion process, providing an additional target for anti-HIV therapeutics, and highlights the need to explore how fusion peptide sequence variations affect receptor-mediated conformational states across diverse HIV strains.
リンク	Cell Rep / PubMed:33238117 / PubMed Central
手法	EM (単粒子)
解像度	3.5 - 4.04 Å
構造データ	20150 6opn EMDB-20150, PDB-6opn: CD4- and 17-bound HIV-1 Env B41 SOSIP in complex with small molecule GO35 手法: EM (単粒子) / 解像度: 3.5 Å 20151 6opo EMDB-20151: C3 symmetry reconstruction of CD4- and 17-bound B41 HIV-1 Env SOSIP in complex with DDM PDB-6opo: Symmetric model of CD4- and 17-bound B41 HIV-1 Env SOSIP in complex with DDM 手法: EM (単粒子) / 解像度: 3.5 Å 20152 6opp EMDB-20152: Asymmetric reconstruction of CD4- and 17-bound B41 HIV-1 Env SOSIP in complex with DDM PDB-6opp: Asymmetric model of CD4- and 17-bound B41 HIV-1 Env SOSIP in complex with DDM 手法: EM (単粒子) / 解像度: 3.7 Å 20153 6opq EMDB-20153: Reconstruction of class 1 of CD4- and 17-bound B41 HIV-1 Env SOSIP incubated with LMNG and small molecule GO27 PDB-6opq: CD4- and 17-bound HIV-1 Env B41 SOSIP frozen with LMNG 手法: EM (単粒子) / 解像度: 3.8 Å 22048 6x5b EMDB-22048: C3 symmetric reconstruction of CD4- and 17-bound B41 HIV-1 Env SOSIP in complex with small molecule GO52 PDB-6x5b: Symmetric model of CD4- and 17-bound B41 HIV-1 Env SOSIP in complex with small molecule GO52 手法: EM (単粒子) / 解像度: 3.6 Å 22049 6x5c EMDB-22049: Asymmetric reconstruction of CD4- and 17b-bound B41 HIV-1 Env SOSIP in complex with small molecule GO52 PDB-6x5c: Asymmetric model of CD4-bound B41 HIV-1 Env SOSIP in complex with small molecule GO52 手法: EM (単粒子) / 解像度: 4.04 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン / N-アセチルグルコサミン ChemComp-N07: [3'-(5-methyl-1,3,4-oxadiazol-2-yl)[1,1'-biphenyl]-3-yl](piperidin-1-yl)methanone ChemComp-LMT: DODECYL-BETA-D-MALTOSIDE / ドデシルβ-D-マルトシド / 可溶化剤YM ChemComp-UOV*: N-(4'-methyl[1,1'-biphenyl]-4-yl)-1-oxa-7-azaspiro[3.5]nonane-7-carboxamide
由来	human immunodeficiency virus 1 (ヒト免疫不全ウイルス) homo sapiens (ヒト)
キーワード	VIRAL PROTEIN/Immune System (ウイルス性) / HIV-1 / Env / CD4 / receptor-bound state / small molecule (小分子) / fusion inhibitor (侵入阻害剤) / VIRAL PROTEIN (ウイルスタンパク質) / VIRAL PROTEIN-Immune System complex (ウイルス性) / detergent (洗剤) / DDM