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	Combining MicroED and native mass spectrometry for structural discovery of enzyme-small molecule complexes.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 122, Issue 31, Page e2503780122, Year 2025
掲載日	2025年8月5日
著者	Niko W Vlahakis / Cameron W Flowers / Mengting Liu / Matthew P Agdanowski / Samuel Johnson / Jacob A Summers / Lian M C Jacobs / Catherine Keyser / Phoebe Russell / Samuel L Rose / Julien Orlans / Nima Adhami / Yu Chen / Michael R Sawaya / Shibom Basu / Daniele de Sanctis / Yu Chen / Soichi Wakatsuki / Hosea M Nelson / Joseph A Loo / Yi Tang / Jose A Rodriguez /
PubMed 要旨	With the goal of accelerating the discovery of small molecule-protein complexes, we leverage fast, low-dose, event-based electron counting microcrystal electron diffraction (MicroED) data collection ...With the goal of accelerating the discovery of small molecule-protein complexes, we leverage fast, low-dose, event-based electron counting microcrystal electron diffraction (MicroED) data collection and native mass spectrometry. This approach, which we term electron diffraction with native mass spectrometry (ED-MS), allows assignment of protein target structures bound to ligands with data obtained from crystal slurries soaked with mixtures of known inhibitors and crude biosynthetic reactions. This extends to libraries of printed ligands dispensed directly onto TEM grids for later soaking with microcrystal slurries, and complexes with noncovalent ligands. ED-MS resolves structures of the natural product, epoxide-based cysteine protease inhibitor E-64, and its biosynthetic analogs bound to the model cysteine protease, papain. It further identifies papain binding to its preferred natural products, by showing that two analogs of E-64 outcompete others in binding to papain crystals, and by detecting papain bound to E-64 and an analog from crude biosynthetic reactions, without purification. ED-MS also resolves binding of the CTX-M-14 β-lactamase, a target of active drug development, to the non-β-lactam inhibitor, avibactam, alone or in a cocktail of unrelated compounds. These results illustrate the utility of ED-MS for natural product ligand discovery and for structure-based screening of small molecule binders to macromolecular targets, promising utility for drug discovery.
リンク	Proc Natl Acad Sci U S A / PubMed:40720654 / PubMed Central
手法	EM (電子線結晶学) / X線回折
解像度	1.4 - 2.8 Å
構造データ	PDB-9nbp: MicroED structure of the papain-E-64 complex from microcrystals mixed on-grid with microarrayed ligand 手法: ELECTRON CRYSTALLOGRAPHY / 解像度: 2.8 Å PDB-9nbq: MicroED structure of papain co-crystallized with E-64D 手法: ELECTRON CRYSTALLOGRAPHY / 解像度: 2.3 Å PDB-9nc1: MicroED structure of papain-E-64 complex from microcrystals soaked with protease inhibitor cocktail 手法: ELECTRON CRYSTALLOGRAPHY / 解像度: 2.4 Å PDB-9nca: MicroED structure of microcrystals soaked with a mixture of E-64, E-64C, and E-64D 手法: ELECTRON CRYSTALLOGRAPHY / 解像度: 2.5 Å PDB-9ncc: Serial synchrotron X-ray diffraction structure of the apo form of papain 手法: X-RAY DIFFRACTION / 解像度: 1.8 Å PDB-9oqe: X-ray diffraction structure of apo-form CTX-M-14 beta-lactamase 手法: X-RAY DIFFRACTION / 解像度: 1.5 Å PDB-9or3: X-ray diffraction structure of CTX-M-14 beta-lactamase co-crystallized with avibactam 手法: X-RAY DIFFRACTION / 解像度: 1.6 Å PDB-9or7: X-ray diffraction structure of CTX-M-14 beta-lactamase soaked with avibactam 手法: X-RAY DIFFRACTION / 解像度: 1.5 Å PDB-9orb: X-ray diffraction structure of the CTX-M-14 beta-lactamase-avibactam complex an inhibitor cocktail-soaked crystal 手法: X-RAY DIFFRACTION / 解像度: 1.5 Å PDB-9org: MicroED structure of apo-form CTX-M-14 beta-lactamase 手法: ELECTRON CRYSTALLOGRAPHY / 解像度: 2.5 Å PDB-9orh: MicroED structure of the CTX-M-14 beta-lactamase-avibactam complex from inhibitor cocktail-soaked crystals 手法: ELECTRON CRYSTALLOGRAPHY / 解像度: 2 Å PDB-9orl: MicroED structure of CTX-M-14 beta-lactamase soaked with avibactam 手法: ELECTRON CRYSTALLOGRAPHY / 解像度: 2.3 Å PDB-9ors: MicroED structure of CTX-M-14 beta-lactamase co-crystallized with avibactam 手法: ELECTRON CRYSTALLOGRAPHY / 解像度: 2 Å PDB-9orv: X-ray diffraction structure of lysozyme co-crystallized with N,N',N"-triacetylchitotriose 手法: X-RAY DIFFRACTION / 解像度: 1.6 Å PDB-9orw: X-ray diffraction structure of apo-form lysozyme 手法: X-RAY DIFFRACTION / 解像度: 1.5 Å PDB-9orx: X-ray diffraction structure of lysozyme complexed with N,N',N"-triacetylchitotriose from a cocktail-soaked crystal 手法: X-RAY DIFFRACTION / 解像度: 1.5 Å PDB-9ory: X-ray diffraction structure of lysozyme soaked with N,N',N"-triacetylchitotriose 手法: X-RAY DIFFRACTION / 解像度: 1.4 Å PDB-9orz: MicroED structure of apo-form lysozyme 手法: ELECTRON CRYSTALLOGRAPHY / 解像度: 2.3 Å PDB-9os0: MicroED structure of lysozyme complexed with N,N',N"-triacetylchitotriose from cocktail-soaked crystals 手法: ELECTRON CRYSTALLOGRAPHY / 解像度: 2.4 Å PDB-9os1: MicroED structure of lysozyme co-crystallized with N,N',N"-triacetylchitotriose 手法: ELECTRON CRYSTALLOGRAPHY / 解像度: 2.3 Å PDB-9os8: MicroED structure of lysozyme soaked with N,N',N"-triacetylchitotriose 手法: ELECTRON CRYSTALLOGRAPHY / 解像度: 2.3 Å
化合物	ChemComp-E64: N-[N-[1-HYDROXYCARBOXYETHYL-CARBONYL]LEUCYLAMINO-BUTYL]-GUANIDINE ChemComp-HOH: WATER ChemComp-E6D: ethyl (3S)-3-hydroxy-4-({(2S)-4-methyl-1-[(3-methylbutyl)amino]-1-oxopentan-2-yl}amino)-4-oxobutanoate ChemComp-E6C: N-[1-HYDROXYCARBOXYETHYL-CARBONYL]LEUCYLAMINO-2-METHYL-BUTANE ChemComp-PO4: PHOSPHATE ION ChemComp-K: Unknown entry ChemComp-NXL: (2S,5R)-1-formyl-5-[(sulfooxy)amino]piperidine-2-carboxamide / 抗生剤, 阻害剤YM ChemComp-GOL: GLYCEROL ChemComp-CL: Unknown entry ChemComp-NA*: Unknown entry
由来	carica papaya (パパイア) escherichia coli (大腸菌) gallus gallus (ニワトリ)
キーワード	HYDROLASE/INHIBITOR / Inhibitor / Complex / MicroED / Enzyme / HYDROLASE-INHIBITOR complex / Cocktail / HYDROLASE / serial / protease / beta-lactamase / ligand