5E2K: Crystal Structure Of Human Carbonic Anhydrase Ii In Complex With The 4-(3-aminophenyl)benzenesulfonamide Inhibitor

Citation:
Abstract
Benzenesulfonamides bearing various substituted (hetero)aryl rings in the para-position were prepared by palladium nanoparticle-catalyzed Suzuki-Miyaura cross-coupling reactions and evaluated as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors against isoforms hCA I, II, IX, and XII. Most of the prepared sulfonamides showed low inhibition against hCA I isoform, whereas the other cytosolic isoenzyme, hCA II, was strongly affected. The major part of these new derivatives acted as potent inhibitors of the tumor-associated isoform hCA XII. An opposite trend was observed for phenyl, naphthyl, and various heteroaryl substituted benzenesulfonamides which displayed subnanomolar hCA IX inhibition while poorly inhibiting the other tumor-associated isoform hCA XII. The inhibition potency and influence of the partially restricted aryl-aryl bond rotation on the activity/selectivity were rationalized by means of X-ray crystallography of the adducts of hCA II with several 4-arylbenzenesulfonamides.
PDB ID: 5E2KDownload
MMDB ID: 135768
PDB Deposition Date: 2015/10/1
Updated in MMDB: 2016/02
Experimental Method:
x-ray diffraction
Resolution: 1.4  Å
Source Organism:
Similar Structures:
Biological Unit for 5E2K: monomeric; determined by author and by software (PISA)
Molecular Components in 5E2K
Label Count Molecule
Protein (1 molecule)
1
Carbonic Anhydrase 2(Gene symbol: CA2)
Molecule annotation
Chemicals (4 molecules)
1
1
2
2
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.