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Figure 5
MicroED and drug discovery. (a) Ligand binding showing the heme group and NADP resolved by MicroED for bovine liver catalase (Nannenga, Shi, Hattne et al., 2014BB80). (b) Drug binding of the inhibitor bevirimat (BVM) in complex with the C-terminal domain of the HIV Gag protein fragment (Purdy et al., 2018BB90). (c) Drug-bound MicroED structure of human carbonic anhydrase isoform II (HCA II) complexed with the clinical drug acetazolamide (AZM) (Clabbers et al., 2020BB15). Inset shows the active site where the ligand is coordinated to the active site zinc metal co-factor. (d) Efficient ligand soaking into microcrystals was demonstrated from lamellae of proteinase K that were briefly soaked on-grid with I3C compounds (Martynowycz & Gonen, 2021aBB70). Four I3C molecules could be identified in the difference map, each difference map is shown next to the observed map of the fitted and refined ligands. (e) Structure of the adenosine A2A-receptor determined from LCP crystals using MicroED (Martynowycz, Shiriaeva et al., 2021BB73). The ligand ZM241385 (ZMA) could be resolved in the orthosteric pocket, as well as four surrounding cholesterol molecules bound to the receptor on the extracellular side. Difference maps are shown next to the refined maps with the fitted ligand and the four numbered cholesterol molecules. In all panels, the positions of the ligand in the protein models are highlighted with yellow rectangular boxes.

IUCrJ
Volume 9| Part 2| March 2022| Pages 169-179
ISSN: 2052-2525
https://doi.org/10.1107/S2052252521013063