6RRI

Human Carbonic Anhydrase II in complex with fluorinated benzenesulfonamide

6RRI の概要

• エントリーDOI: 10.2210/pdb6rri/pdb
• 関連するPDBエントリー: 6RIT 6RJJ 6RKN 6RNP 6ROE 6RQI 6RRG
• 分子名称: Carbonic anhydrase 2, ZINC ION, MERCURY (II) ION, ... (8 entities in total)
• 機能のキーワード: inhibitor, complex, co2 conversion, lyase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31248.36

構造登録者

Gloeckner, S.,Heine, A.,Klebe, G. (登録日: 2019-05-18, 公開日: 2020-04-15, 最終更新日: 2024-01-24)

主引用文献

Glockner, S.,Ngo, K.,Wagner, B.,Heine, A.,Klebe, G.
The Influence of Varying Fluorination Patterns on the Thermodynamics and Kinetics of Benzenesulfonamide Binding to Human Carbonic Anhydrase II.
Biomolecules, 10:-, 2020

PubMed Abstract: The fluorination of lead-like compounds is a common tool in medicinal chemistry to alter molecular properties in various ways and with different goals. We herein present a detailed study of the binding of fluorinated benzenesulfonamides to human Carbonic Anhydrase II by complementing macromolecular X-ray crystallographic observations with thermodynamic and kinetic data collected with the novel method of kinITC. Our findings comprise so far unknown alternative binding modes in the crystalline state for some of the investigated compounds as well as complex thermodynamic and kinetic structure-activity relationships. They suggest that fluorination of the benzenesulfonamide core is especially advantageous in one position with respect to the kinetic signatures of binding and that a higher degree of fluorination does not necessarily provide for a higher affinity or more favorable kinetic binding profiles. Lastly, we propose a relationship between the kinetics of binding and ligand acidity based on a small set of compounds with similar substitution patterns.

PubMed: 32230853
DOI: 10.3390/biom10040509

実験手法

X-RAY DIFFRACTION (1.097 Å)