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	Cryo-EM structure determination of small therapeutic protein targets at 3 Å-resolution using a rigid imaging scaffold.
Journal, issue, pages	Proc Natl Acad Sci U S A, Vol. 120, Issue 37, Page e2305494120, Year 2023
Publish date	Sep 12, 2023
Authors	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 Abstract	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.
External links	Proc Natl Acad Sci U S A / PubMed:37669364 / PubMed Central
Methods	EM (single particle)
Resolution	2.2 - 3.19 Å
Structure data	29700 8g3k EMDB-29700, PDB-8g3k: Cryo-EM imaging scaffold subunits A and B used to display KRAS G12C complex with GDP Method: EM (single particle) / Resolution: 2.2 Å 29713 8g42 EMDB-29713, PDB-8g42: KRAS G12C complex with GDP imaged on a cryo-EM imaging scaffold Method: EM (single particle) / Resolution: 3.02 Å 29715 8g47 EMDB-29715, PDB-8g47: KRAS G12C complex with GDP and AMG 510 imaged on a cryo-EM imaging scaffold Method: EM (single particle) / Resolution: 3.19 Å 29718 8g4e EMDB-29718, PDB-8g4e: Green Fluorescence Protein imaged on a cryo-EM imaging scaffold Method: EM (single particle) / Resolution: 2.98 Å 29719 8g4f EMDB-29719, PDB-8g4f: KRAS G12V complex with GDP imaged on a cryo-EM imaging scaffold Method: EM (single particle) / Resolution: 2.91 Å 29720 8g4h EMDB-29720, PDB-8g4h: KRAS G13C complex with GDP imaged on a cryo-EM imaging scaffold Method: EM (single particle) / Resolution: 2.87 Å
Chemicals	ChemComp-GDP: GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying moleculeYM ChemComp-MG: Unknown entry ChemComp-MOV: AMG 510 (bound form) ChemComp-HOH*: WATER
Source	synthetic construct (others) thermoplasma acidophilum (acidophilic) homo sapiens (human) aequorea victoria (jellyfish)
Keywords	STRUCTURAL PROTEIN / CryoEM imaging scaffold / Cancer / GTPase / SIGNALING PROTEIN