6YMA

MicroED structure of acetazolamide-bound human carbonic anhydrase II

Summary for 6YMA

• Entry DOI: 10.2210/pdb6yma/pdb
• Descriptor: carbonic anhydrase 2, ZINC ION, 5-ACETAMIDO-1,3,4-THIADIAZOLE-2-SULFONAMIDE, ... (5 entities in total)
• Functional Keywords: carbonic anhydrase, acetazolamide, inhibitor complex, microed, lyase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 29654.85

Authors

Clabbers, M.T.B.,Fisher, S.Z.,Coincon, M.,Zou, X.,Xu, H. (deposition date: 2020-04-08, release date: 2020-08-12, Last modification date: 2024-01-24)

Primary citation

Clabbers, M.T.B.,Fisher, S.Z.,Coincon, M.,Zou, X.,Xu, H.
Visualizing drug binding interactions using microcrystal electron diffraction.
Commun Biol, 3:417-417, 2020

PubMed Abstract: Visualizing ligand binding interactions is important for structure-based drug design and fragment-based screening methods. Rapid and uniform soaking with potentially reduced lattice defects make small macromolecular crystals attractive targets for studying drug binding using microcrystal electron diffraction (MicroED). However, so far no drug binding interactions could unambiguously be resolved by electron diffraction alone. Here, we use MicroED to study the binding of a sulfonamide inhibitor to human carbonic anhydrase isoform II (HCA II). We show that MicroED data can efficiently be collected on a conventional transmission electron microscope from thin hydrated microcrystals soaked with the clinical drug acetazolamide (AZM). The data are of high enough quality to unequivocally fit and resolve the bound inhibitor. We anticipate MicroED can play an important role in facilitating in-house fragment screening for drug discovery, complementing existing methods in structural biology such as X-ray and neutron diffraction.

PubMed: 32737395
DOI: 10.1038/s42003-020-01155-1

Experimental method

ELECTRON CRYSTALLOGRAPHY (2.5 Å)