3IBN

The crystal structure of the human carbonic anhydrase II in complex with an aliphatic bis-sulfamate inhibitor

3IBN の概要

• エントリーDOI: 10.2210/pdb3ibn/pdb
• 関連するPDBエントリー: 1CA2 3IBI 3IBL 3IBU
• 分子名称: Carbonic anhydrase 2, ZINC ION, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: carbonic anhydrase ii, protein-inhibitor complex, aliphatic bis-sulfamate inhibitor, disease mutation, metal-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: 29929.87

構造登録者

Alterio, V.,De Simone, G. (登録日: 2009-07-16, 公開日: 2009-09-22, 最終更新日: 2023-11-01)

主引用文献

Vitale, R.M.,Alterio, V.,Innocenti, A.,Winum, J.-Y.,Monti, S.M.,De Simone, G.,Supuran, C.T.
Carbonic anhydrase inhibitors. Comparison of aliphatic sulfamate/bis-sulfamate adducts with isozymes II and IX as a platform for designing tight-binding, more isoform-selective inhibitors
J.Med.Chem., 52:5990-5998, 2009

PubMed Abstract: Two approaches were used to design inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1): the tail and the ring approaches. Aliphatic sulfamates constitute a class of CA inhibitors (CAIs) that cannot be classified in either one of these categories. We report here the detailed inhibition profile of four such compounds against isoforms CAs I-XIV, the first crystallographic structures of these compounds in adduct with isoform II, and molecular modeling studies for their interaction with hCA IX. Aliphatic monosulfamates/bis-sulfamates were nanomolar inhibitors of hCAs II, IX, and XII, unlike aromatic/heterocyclic sulfonamides that promiscuously inhibit most CA isozymes with low nanomolar affinity. The bis-sulfamates incorporating 8 or 10 carbon atoms showed higher affinity for the tumor-associated hCA IX compared to hCA II, whereas the opposite was true for the monosulfamates. The explanation for their interaction with CA active site furnishes insights for obtaining compounds with increased affinity/selectivity for various isozymes.

PubMed: 19731956
DOI: 10.1021/jm900641r

実験手法

X-RAY DIFFRACTION (2.2 Å)