3MHC: Crystal Structure Of Human Cabonic Anhydrase Ii In Adduct With An Adamantyl Analogue Of Acetazolamide In A Novel Hydrophobic Binding Pocket

Citation:
Abstract
We investigated the inhibitory activity of several 1,3,4-thiadiazole-sulfonamides against all catalytically active CA (EC 4.2.1.1), CA I-XV. The tail derivatizing the 5-position in the 1,3,4-thiadiazole-2-sulfonamide scaffold was observed to be critical as an inhibitory determinant of these compounds. The high resolution X-ray crystal structure of hCA II in complex with 5-(1-adamantylcarboxamido)-1,3,4-thiadiazole-2-sulfonamide, showed the adamantyl moiety of the inhibitor residing in a less utilized binding pocket than that of most hydrophobic inhibitors, lined by the amino acid residues Ile91, Val121 and Phe131. This binding site may explain the diverse inhibition profiles of 5-carboxamide- and sufonamide-derivatized 1,3,4-thiadiazole-2-sulfonamides and offers a hot spot for designing isoform selective inhibitors, considering that residues 91 and 131 are highly variable among the 13 catalytically active isoforms.
PDB ID: 3MHCDownload
MMDB ID: 83504
PDB Deposition Date: 2010/4/7
Updated in MMDB: 2010/07
Experimental Method:
x-ray diffraction
Resolution: 1.7  Å
Source Organism:
Similar Structures:
Biological Unit for 3MHC: monomeric; determined by author and by software (PISA)
Molecular Components in 3MHC
Label Count Molecule
Protein (1 molecule)
1
Carbonic Anhydrase 2(Gene symbol: CA2)
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.