Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Combining MicroED and native mass spectrometry for structural discovery of enzyme-small molecule complexes.
Journal, issue, pages	Proc Natl Acad Sci U S A, Vol. 122, Issue 31, Page e2503780122, Year 2025
Publish date	Aug 5, 2025
Authors	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 Abstract	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.
External links	Proc Natl Acad Sci U S A / PubMed:40720654 / PubMed Central
Methods	EM (electron crystallography) / X-ray diffraction
Resolution	1.4 - 2.8 Å
Structure data	PDB-9nbp: MicroED structure of the papain-E-64 complex from microcrystals mixed on-grid with microarrayed ligand Method: ELECTRON CRYSTALLOGRAPHY / Resolution: 2.8 Å PDB-9nbq: MicroED structure of papain co-crystallized with E-64D Method: ELECTRON CRYSTALLOGRAPHY / Resolution: 2.3 Å PDB-9nc1: MicroED structure of papain-E-64 complex from microcrystals soaked with protease inhibitor cocktail Method: ELECTRON CRYSTALLOGRAPHY / Resolution: 2.4 Å PDB-9nca: MicroED structure of microcrystals soaked with a mixture of E-64, E-64C, and E-64D Method: ELECTRON CRYSTALLOGRAPHY / Resolution: 2.5 Å PDB-9ncc: Serial synchrotron X-ray diffraction structure of the apo form of papain Method: X-RAY DIFFRACTION / Resolution: 1.8 Å PDB-9oqe: X-ray diffraction structure of apo-form CTX-M-14 beta-lactamase Method: X-RAY DIFFRACTION / Resolution: 1.5 Å PDB-9or3: X-ray diffraction structure of CTX-M-14 beta-lactamase co-crystallized with avibactam Method: X-RAY DIFFRACTION / Resolution: 1.6 Å PDB-9or7: X-ray diffraction structure of CTX-M-14 beta-lactamase soaked with avibactam Method: X-RAY DIFFRACTION / Resolution: 1.5 Å PDB-9orb: X-ray diffraction structure of the CTX-M-14 beta-lactamase-avibactam complex an inhibitor cocktail-soaked crystal Method: X-RAY DIFFRACTION / Resolution: 1.5 Å PDB-9org: MicroED structure of apo-form CTX-M-14 beta-lactamase Method: ELECTRON CRYSTALLOGRAPHY / Resolution: 2.5 Å PDB-9orh: MicroED structure of the CTX-M-14 beta-lactamase-avibactam complex from inhibitor cocktail-soaked crystals Method: ELECTRON CRYSTALLOGRAPHY / Resolution: 2 Å PDB-9orl: MicroED structure of CTX-M-14 beta-lactamase soaked with avibactam Method: ELECTRON CRYSTALLOGRAPHY / Resolution: 2.3 Å PDB-9ors: MicroED structure of CTX-M-14 beta-lactamase co-crystallized with avibactam Method: ELECTRON CRYSTALLOGRAPHY / Resolution: 2 Å PDB-9orv: X-ray diffraction structure of lysozyme co-crystallized with N,N',N"-triacetylchitotriose Method: X-RAY DIFFRACTION / Resolution: 1.6 Å PDB-9orw: X-ray diffraction structure of apo-form lysozyme Method: X-RAY DIFFRACTION / Resolution: 1.5 Å PDB-9orx: X-ray diffraction structure of lysozyme complexed with N,N',N"-triacetylchitotriose from a cocktail-soaked crystal Method: X-RAY DIFFRACTION / Resolution: 1.5 Å PDB-9ory: X-ray diffraction structure of lysozyme soaked with N,N',N"-triacetylchitotriose Method: X-RAY DIFFRACTION / Resolution: 1.4 Å PDB-9orz: MicroED structure of apo-form lysozyme Method: ELECTRON CRYSTALLOGRAPHY / Resolution: 2.3 Å PDB-9os0: MicroED structure of lysozyme complexed with N,N',N"-triacetylchitotriose from cocktail-soaked crystals Method: ELECTRON CRYSTALLOGRAPHY / Resolution: 2.4 Å PDB-9os1: MicroED structure of lysozyme co-crystallized with N,N',N"-triacetylchitotriose Method: ELECTRON CRYSTALLOGRAPHY / Resolution: 2.3 Å PDB-9os8: MicroED structure of lysozyme soaked with N,N',N"-triacetylchitotriose Method: ELECTRON CRYSTALLOGRAPHY / Resolution: 2.3 Å
Chemicals	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 / antibioticYM ChemComp-GOL: GLYCEROL ChemComp-CL: Unknown entry ChemComp-NA*: Unknown entry
Source	carica papaya (papaya) escherichia coli (E. coli) gallus gallus (chicken)
Keywords	HYDROLASE/INHIBITOR / Inhibitor / Complex / MicroED / Enzyme / HYDROLASE-INHIBITOR complex / Cocktail / HYDROLASE / serial / protease / beta-lactamase / ligand