5TT8

Crystal structure of the complex of Helicobacter pylori alpha-carbonic anhydrase with benzolamide

5TT8 の概要

• エントリーDOI: 10.2210/pdb5tt8/pdb
• 関連するPDBエントリー: 5TT3 5TUO 5TV3
• 分子名称: Alpha-carbonic anhydrase, ZINC ION, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: alpha-carbonic anhydrase, helicobacter pylori, zinc metalloenzyme, lyase
• 由来する生物種: Helicobacter pylori (strain ATCC 700392 / 26695)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 219012.53

構造登録者

Modak, J.K.,Roujeinikova, A. (登録日: 2016-11-02, 公開日: 2017-09-13, 最終更新日: 2024-10-16)

主引用文献

Modak, J.K.,Liu, Y.C.,Supuran, C.T.,Roujeinikova, A.
Structure-Activity Relationship for Sulfonamide Inhibition of Helicobacter pylori alpha-Carbonic Anhydrase.
J. Med. Chem., 59:11098-11109, 2016

PubMed Abstract: α-Carbonic anhydrase of Helicobacter pylori (HpαCA) plays an important role in the acclimation of this oncobacterium to the acidic pH of the stomach. Sulfonamide inhibitors of HpαCA possess anti-H. pylori activity. The crystal structures of complexes of HpαCA with a family of acetazolamide-related sulfonamides have been determined. Analysis of the structures revealed that the mode of sulfonamide binding correlates well with their inhibitory activities. In addition, comparisons with the corresponding inhibitor complexes of human carbonic anhydrase II (HCAII) indicated that HpαCA possesses an additional, alternative binding site for sulfonamides that is not present in HCAII. Furthermore, the hydrophobic pocket in HCAII that stabilizes the apolar moiety of sulfonamide inhibitors is replaced with a more open, hydrophilic pocket in HpαCA. Thus, our analysis identified major structural features can be exploited in the design of selective and more potent inhibitors of HpαCA that may lead to novel antimicrobials.

PubMed: 28002963
DOI: 10.1021/acs.jmedchem.6b01333

実験手法

X-RAY DIFFRACTION (2.4 Å)