4PQ7

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

4PQ7 の概要

• エントリーDOI: 10.2210/pdb4pq7/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, 1-but-2-ynoxy-4-[(sulfamoylamino)methyl]benzene, ... (5 entities in total)
• 機能のキーワード: sulfamide, zinc binding, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P00918
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30143.42

構造登録者

Alterio, V.,De Simone, G. (登録日: 2014-02-28, 公開日: 2014-10-08, 最終更新日: 2023-09-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.85 Å)