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	Binding adaptability of chemical ligands to polymorphic α-synuclein amyloid fibrils.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 121, Issue 35, Page e2321633121, Year 2024
掲載日	2024年8月27日
著者	Kaien Liu / Youqi Tao / Qinyue Zhao / Wencheng Xia / Xiang Li / Shenqing Zhang / Yuxuan Yao / Huaijiang Xiang / Chao Han / Li Tan / Bo Sun / Dan Li / Ang Li / Cong Liu /
PubMed 要旨	α-synuclein (α-syn) assembles into structurally distinct fibril polymorphs seen in different synucleinopathies, such as Parkinson's disease and multiple system atrophy. Targeting these unique ...α-synuclein (α-syn) assembles into structurally distinct fibril polymorphs seen in different synucleinopathies, such as Parkinson's disease and multiple system atrophy. Targeting these unique fibril structures using chemical ligands holds diagnostic significance for different disease subtypes. However, the molecular mechanisms governing small molecules interacting with different fibril polymorphs remain unclear. Here, we investigated the interactions of small molecules belonging to four distinct scaffolds, with different α-syn fibril polymorphs. Using cryo-electron microscopy, we determined the structures of these molecules when bound to the fibrils formed by E46K mutant α-syn and compared them to those bound with wild-type α-syn fibrils. Notably, we observed that these ligands exhibit remarkable binding adaptability, as they engage distinct binding sites across different fibril polymorphs. While the molecular scaffold primarily steered the binding locations and geometries on specific sites, the conjugated functional groups further refined this adaptable binding by fine-tuning the geometries and binding sites. Overall, our finding elucidates the adaptability of small molecules binding to different fibril structures, which sheds light on the diagnostic tracer and drug developments tailored to specific pathological fibril polymorphs.
リンク	Proc Natl Acad Sci U S A / PubMed:39172784 / PubMed Central
手法	EM (らせん対称)
解像度	2.7 - 3.5 Å
構造データ	38097 8x7b EMDB-38097, PDB-8x7b: ThT-bound E46K alpha-synuclein fibrils 手法: EM (らせん対称) / 解像度: 3.0 Å 38103 8x7l EMDB-38103, PDB-8x7l: EB-bound E46K alpha-synuclein fibrils 手法: EM (らせん対称) / 解像度: 3.4 Å 38104 8x7m EMDB-38104, PDB-8x7m: CR-bound E46K alpha-synuclein fibrils 手法: EM (らせん対称) / 解像度: 3.0 Å 38105 8x7o EMDB-38105, PDB-8x7o: PiB-bound E46K mutanted alpha-synuclein fibrils 手法: EM (らせん対称) / 解像度: 3.5 Å 38106 8x7p EMDB-38106, PDB-8x7p: CCA-bound E46K alpha-synuclein fibrils 手法: EM (らせん対称) / 解像度: 2.7 Å 38107 8x7q EMDB-38107, PDB-8x7q: pFTAA-bound E46K alpha-synuclein fibrils 手法: EM (らせん対称) / 解像度: 2.7 Å 38108 8x7r EMDB-38108, PDB-8x7r: C05-03-bound E46K alpha-synuclein fibrils 手法: EM (らせん対称) / 解像度: 3.0 Å 60226 8zli EMDB-60226, PDB-8zli: BTA-2-bound E46K alpha-synuclein fibrils 手法: EM (らせん対称) / 解像度: 3.4 Å 60231 8zlo EMDB-60231, PDB-8zlo: F0502B-bound E46K alpha-synuclein fibril 手法: EM (らせん対称) / 解像度: 3.1 Å 60232 8zlp EMDB-60232, PDB-8zlp: apo WT polymorph 5a alpha-synuclein fibril 手法: EM (らせん対称) / 解像度: 3.5 Å 60262 8zmy EMDB-60262, PDB-8zmy: F0502B-bound WT polymorph 5a alpha-synuclein fibril 手法: EM (らせん対称) / 解像度: 2.9 Å
化合物	ChemComp-TFX: 2-[4-(dimethylamino)phenyl]-3,6-dimethyl-1,3-benzothiazol-3-ium / 2-[4-(ジメチルアミノ)フェニル]-3,6-ジメチルベンゾチアゾ-ル-3-イウム ChemComp-IZ8: 4-azanyl-6-[[4-[4-[(~{E})-(8-azanyl-1-oxidanyl-5,7-disulfo-naphthalen-2-yl)diazenyl]-3-methyl-phenyl]-2-methyl-phenyl]diazenyl]-5-oxidanyl-naphthalene-1,3-disulfonic acid / 6,6′-[(3,3′-ジメチル-4,4′-ビフェニリレン)ビスアゾ]ビス(4-アミノ-5-ヒドロキシナフタレン-1,(以下略) ChemComp-CGO: sodium 3,3'-(1E,1'E)-biphenyl-4,4'-diylbis(diazene-2,1-diyl)bis(4-aminonaphthalene-1-sulfonate) / コンゴ-レッド ChemComp-IZV: 2-[4-(methylamino)phenyl]-1,3-benzothiazol-6-ol / ピッツバ-グ化合物B ChemComp-V79: copper;trisodium;18-(2-carboxylatoethyl)-20-(carboxylatomethyl)-12-ethenyl-7-ethyl-3,8,13,17-tetramethyl-17,18-dihydroporphyrin-21,23-diide-2-carboxylate ChemComp-3LS: 3''',4'-bis(carboxymethyl)-2,2':5',2'':5'',2''':5''',2''''-quinquethiophene-5,5''''-dicarboxylic acid / 4′,3′′′-ビス(カルボキシメチル)-2,2′:5′,2′′:5′′,2′′′:5′′′,2′′′′-キンクエチオ(以下略) 化合物画像なし ChemComp-Y9W: Unknown entry PDB-1l13: CONTRIBUTIONS OF HYDROGEN BONDS OF THR 157 TO THE THERMODYNAMIC STABILITY OF PHAGE T4 LYSOZYME ChemComp-1KI: 2-bromanyl-4-[(~{E})-2-[6-[2-(2-fluoranylethoxy)ethyl-methyl-amino]-5-methyl-1,3-benzothiazol-2-yl]ethenyl]phenol
由来	homo sapiens (ヒト)
キーワード	PROTEIN FIBRIL / amyloid fibril / complex