8DJ9

Carbonic Anhydrase II in complex with Ibuprofen

Summary for 8DJ9

• Entry DOI: 10.2210/pdb8dj9/pdb
• Descriptor: Carbonic anhydrase 2, GLYCEROL, (2R)-2-[4-(2-methylpropyl)phenyl]propanoic acid, ... (6 entities in total)
• Functional Keywords: carbonic anhydrase, ibuprofen inhibitor, metal binding protein, lyase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 29989.23

Authors

Combs, J.C.,McKenna, R.,Andring, J.T. (deposition date: 2022-06-30, release date: 2022-11-09, Last modification date: 2024-05-01)

Primary citation

Combs, J.,Andring, J.,McKenna, R.
Ibuprofen: a weak inhibitor of carbonic anhydrase II.
Acta Crystallogr.,Sect.F, 78:395-402, 2022

PubMed Abstract: Carbonic anhydrases (CAs) are drug targets for a variety of diseases. While many clinically relevant CA inhibitors are sulfonamide-based, novel CA inhibitors are being developed that incorporate alternative zinc-binding groups, such as carboxylic acid moieties, to develop CA isoform-specific inhibitors. Here, the X-ray crystal structure of human CA II (hCA II) in complex with the carboxylic acid ibuprofen [2-(4-isobutylphenyl)propanoic acid, a common over-the-counter nonsteroidal anti-inflammatory drug] is reported to 1.54 Å resolution. The binding of ibuprofen is overlaid with the structures of other carboxylic acids in complex with hCA II to compare their inhibition mechanisms by direct or indirect (via a water) binding to the active-site zinc. Additionally, enzyme-inhibition assays using ibuprofen, nicotinic acid and ferulic acid were performed with hCA II to determine their IC values and were compared with those of other carboxylic acid binders. This study discusses the potential development of CA inhibitors utilizing the carboxylic acid moiety.

PubMed: 36322425
DOI: 10.1107/S2053230X22009761

Experimental method

X-RAY DIFFRACTION (1.54 Å)