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	Cryo-EM structure determination of small therapeutic protein targets at 3 Å-resolution using a rigid imaging scaffold.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 120, Issue 37, Page e2305494120, Year 2023
掲載日	2023年9月12日
著者	Roger Castells-Graells / Kyle Meador / Mark A Arbing / Michael R Sawaya / Morgan Gee / Duilio Cascio / Emma Gleave / Judit É Debreczeni / Jason Breed / Karoline Leopold / Ankoor Patel / Dushyant Jahagirdar / Bronwyn Lyons / Sriram Subramaniam / Chris Phillips / Todd O Yeates /
PubMed 要旨	Cryoelectron microscopy (Cryo-EM) has enabled structural determination of proteins larger than about 50 kDa, including many intractable by any other method, but it has largely failed for smaller ...Cryoelectron microscopy (Cryo-EM) has enabled structural determination of proteins larger than about 50 kDa, including many intractable by any other method, but it has largely failed for smaller proteins. Here, we obtain structures of small proteins by binding them to a rigid molecular scaffold based on a designed protein cage, revealing atomic details at resolutions reaching 2.9 Å. We apply this system to the key cancer signaling protein KRAS (19 kDa in size), obtaining four structures of oncogenic mutational variants by cryo-EM. Importantly, a structure for the key G12C mutant bound to an inhibitor drug (AMG510) reveals significant conformational differences compared to prior data in the crystalline state. The findings highlight the promise of cryo-EM scaffolds for advancing the design of drug molecules against small therapeutic protein targets in cancer and other human diseases.
リンク	Proc Natl Acad Sci U S A / PubMed:37669364 / PubMed Central
手法	EM (単粒子)
解像度	2.2 - 3.19 Å
構造データ	29700 8g3k EMDB-29700, PDB-8g3k: Cryo-EM imaging scaffold subunits A and B used to display KRAS G12C complex with GDP 手法: EM (単粒子) / 解像度: 2.2 Å 29713 8g42 EMDB-29713, PDB-8g42: KRAS G12C complex with GDP imaged on a cryo-EM imaging scaffold 手法: EM (単粒子) / 解像度: 3.02 Å 29715 8g47 EMDB-29715, PDB-8g47: KRAS G12C complex with GDP and AMG 510 imaged on a cryo-EM imaging scaffold 手法: EM (単粒子) / 解像度: 3.19 Å 29718 8g4e EMDB-29718, PDB-8g4e: Green Fluorescence Protein imaged on a cryo-EM imaging scaffold 手法: EM (単粒子) / 解像度: 2.98 Å 29719 8g4f EMDB-29719, PDB-8g4f: KRAS G12V complex with GDP imaged on a cryo-EM imaging scaffold 手法: EM (単粒子) / 解像度: 2.91 Å 29720 8g4h EMDB-29720, PDB-8g4h: KRAS G13C complex with GDP imaged on a cryo-EM imaging scaffold 手法: EM (単粒子) / 解像度: 2.87 Å
化合物	ChemComp-GDP: GUANOSINE-5'-DIPHOSPHATE / GDP / GDP, エネルギー貯蔵分子YM ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-MOV: AMG 510 (bound form) ChemComp-HOH*: WATER
由来	synthetic construct (人工物) thermoplasma acidophilum (好酸性) homo sapiens (ヒト) aequorea victoria (オワンクラゲ)
キーワード	STRUCTURAL PROTEIN / CryoEM imaging scaffold / Cancer / GTPase / SIGNALING PROTEIN