5BYI

Human carbonic anhydrase II with an azobenzene inhibitor (1d)

Summary for 5BYI

• Entry DOI: 10.2210/pdb5byi/pdb
• Related: 2VVA
• Descriptor: Carbonic anhydrase 2, ZINC ION, 4-(HYDROXYMERCURY)BENZOIC ACID, ... (6 entities in total)
• Functional Keywords: carbonic anhydrase, sulfonamide, photopharmacology, inhibitor, lyase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : P00918
• Total number of polymer chains: 1
• Total formula weight: 30047.69

Authors

Groll, M.,Broichhagen, J. (deposition date: 2015-06-10, release date: 2015-08-05, Last modification date: 2024-05-08)

Primary citation

Runtsch, L.S.,Barber, D.M.,Mayer, P.,Groll, M.,Trauner, D.,Broichhagen, J.
Azobenzene-based inhibitors of human carbonic anhydrase II.
Beilstein J Org Chem, 11:1129-1135, 2015

PubMed Abstract: Aryl sulfonamides are a widely used drug class for the inhibition of carbonic anhydrases. In the context of our program of photochromic pharmacophores we were interested in the exploration of azobenzene-containing sulfonamides to block the catalytic activity of human carbonic anhydrase II (hCAII). Herein, we report the synthesis and in vitro evaluation of a small library of nine photochromic sulfonamides towards hCAII. All molecules are azobenzene-4-sulfonamides, which are substituted by different functional groups in the 4´-position and were characterized by X-ray crystallography. We aimed to investigate the influence of electron-donating or electron-withdrawing substituents on the inhibitory constant K i. With the aid of an hCAII crystal structure bound to one of the synthesized azobenzenes, we found that the electronic structure does not strongly affect inhibition. Taken together, all compounds are strong blockers of hCAII with K i = 25-65 nM that are potentially photochromic and thus combine studies from chemical synthesis, crystallography and enzyme kinetics.

PubMed: 26199669
DOI: 10.3762/bjoc.11.127

Experimental method

X-RAY DIFFRACTION (1.15 Å)