3NB5

Human carbonic anhydrase II in complex with 2-(3-chloro-4-hydroxyphenyl)-N-(4-sulfamoylphenethyl)acetamide

3NB5 の概要

• エントリーDOI: 10.2210/pdb3nb5/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, 2-(3-chloro-4-hydroxyphenyl)-N-[2-(4-sulfamoylphenyl)ethyl]acetamide, ... (5 entities in total)
• 機能のキーワード: drug design, natural product, sulfamate, 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: 29999.59

構造登録者

Hofmann, A.,Osman, A.,Davis, R.A. (登録日: 2010-06-02, 公開日: 2011-04-20, 最終更新日: 2023-11-01)

主引用文献

Davis, R.A.,Hofmann, A.,Osman, A.,Hall, R.A.,Muhlschlegel, F.A.,Vullo, D.,Innocenti, A.,Supuran, C.T.,Poulsen, S.A.
Natural Product-Based Phenols as Novel Probes for Mycobacterial and Fungal Carbonic Anhydrases
J.Med.Chem., 54:1682-1692, 2011

PubMed Abstract: In order to discover novel probes that may help in the investigation and control of infectious diseases through a new mechanism of action, we have evaluated a library of phenol-based natural products (NPs) for enzyme inhibition against four recently characterized pathogen β-family carbonic anhydrases (CAs). These include CAs from Mycobacterium tuberculosis, Candida albicans, and Cryptococcus neoformans as well as α-family human CA I and CA II for comparison. Many of the NPs selectively inhibited the mycobacterial and fungal β-CAs, with the two best performing compounds displaying submicromolar inhibition with a preference for fungal over human CA inhibition of more than 2 orders of magnitude. These compounds provide the first example of non-sulfonamide inhibitors that display β over α CA enzyme selectivity. Structural characterization of the library compounds in complex with human CA II revealed a novel binding mode whereby a methyl ester interacts via a water molecule with the active site zinc.

PubMed: 21332115
DOI: 10.1021/jm1013242

実験手法

X-RAY DIFFRACTION (1.8 Å)