4PQ7

The crystal structure of the human carbonic anhydrase ii in complex with a sulfamide inhibitor

Summary for 4PQ7

• Entry DOI: 10.2210/pdb4pq7/pdb
• Descriptor: Carbonic anhydrase 2, ZINC ION, 1-but-2-ynoxy-4-[(sulfamoylamino)methyl]benzene, ... (5 entities in total)
• Functional Keywords: sulfamide, zinc binding, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P00918
• Total number of polymer chains: 1
• Total formula weight: 30143.42

Authors

Alterio, V.,De Simone, G. (deposition date: 2014-02-28, release date: 2014-10-08, Last modification date: 2023-09-20)

Primary citation

De Simone, G.,Pizika, G.,Monti, S.M.,Di Fiore, A.,Ivanova, J.,Vozny, I.,Trapencieris, P.,Zalubovskis, R.,Supuran, C.T.,Alterio, V.
Hydrophobic substituents of the phenylmethylsulfamide moiety can be used for the development of new selective carbonic anhydrase inhibitors.
Biomed Res Int, 2014:523210-523210, 2014

PubMed Abstract: A new series of compounds containing a sulfamide moiety as zinc-binding group (ZBG) has been synthesized and tested for determining inhibitory properties against four human carbonic anhydrase (hCA) isoforms, namely, CAs I, II, IX, and XII. The X-ray structure of the cytosolic dominant isoform hCA II in complex with the best inhibitor of the series has also been determined providing further insights into sulfamide binding mechanism and confirming that such zinc-binding group, if opportunely derivatized, can be usefully exploited for obtaining new potent and selective CAIs. The analysis of the structure also suggests that for drug design purposes the but-2-yn-1-yloxy moiety tail emerges as a very interesting substituent of the phenylmethylsulfamide moiety due to its capability to establish strong van der Waals interactions with a hydrophobic cleft on the hCA II surface, delimited by residues Phe131, Val135, Pro202, and Leu204. Indeed, the complementarity of this tail with the cleft suggests that different substituents could be used to discriminate between isoforms having clefts with different sizes.

PubMed: 25258712
DOI: 10.1155/2014/523210

Experimental method

X-RAY DIFFRACTION (1.85 Å)