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-Structure paper
Title | Fragment-based drug discovery using cryo-EM. |
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Journal, issue, pages | Drug Discov Today, Vol. 25, Issue 3, Page 485-490, Year 2020 |
Publish date | Dec 23, 2019 |
![]() | Michael Saur / Michael J Hartshorn / Jing Dong / Judith Reeks / Gabor Bunkoczi / Harren Jhoti / Pamela A Williams / ![]() |
PubMed Abstract | Recent advances in electron cryo-microscopy (cryo-EM) structure determination have pushed the resolutions obtainable by the method into the range widely considered to be of utility for drug discovery. ...Recent advances in electron cryo-microscopy (cryo-EM) structure determination have pushed the resolutions obtainable by the method into the range widely considered to be of utility for drug discovery. Here, we review the use of cryo-EM in fragment-based drug discovery (FBDD) based on in-house method development. We demonstrate not only that cryo-EM can reveal details of the molecular interactions between fragments and a protein, but also that the current reproducibility, quality, and throughput are compatible with FBDD. We exemplify this using the test system β-galactosidase (Bgal) and the oncology target pyruvate kinase 2 (PKM2). |
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Methods | EM (single particle) |
Resolution | 2.2 - 3.2 Å |
Structure data | EMDB-10563, PDB-6tsh: EMDB-10564, PDB-6tsk: EMDB-10574, PDB-6tte: EMDB-10575, PDB-6ttf: EMDB-10576, PDB-6tth: EMDB-10577, PDB-6tti: EMDB-10584, PDB-6ttq: |
Chemicals | ![]() ChemComp-MG: ![]() ChemComp-DGJ: ![]() ChemComp-HOH: ![]() ChemComp-0MK: ![]() ChemComp-PTQ: ![]() ChemComp-LZ2: ![]() ChemComp-FBP: ![]() ChemComp-THR: ![]() ChemComp-NXE: ![]() ChemComp-DMS: ![]() ChemComp-NXH: |
Source |
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![]() | SUGAR BINDING PROTEIN / Bgal / nojirimycin / L-ribose / ![]() ![]() ![]() |