6I3E

Human Carbonic Anhydrase II in complex with 4-Butylbenzenesulfonamide

6I3E の概要

• エントリーDOI: 10.2210/pdb6i3e/pdb
• 関連するPDBエントリー: 6GDC 6GM9 6HQX 6HR3 6HXD 6I0W 6I1U 6I2F
• 分子名称: Carbonic anhydrase 2, ZINC ION, DIMETHYL SULFOXIDE, ... (9 entities in total)
• 機能のキーワード: lyase, inhibitor, complex, co2 conversion
• 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: 31247.25

構造登録者

Gloeckner, S.,Ngo, K.,Heine, A.,Klebe, G. (登録日: 2018-11-05, 公開日: 2019-11-20, 最終更新日: 2024-01-24)

主引用文献

Glockner, S.,Ngo, K.,Sager, C.P.,Hufner-Wulsdorf, T.,Heine, A.,Klebe, G.
Conformational Changes in Alkyl Chains Determine the Thermodynamic and Kinetic Binding Profiles of Carbonic Anhydrase Inhibitors.
Acs Chem.Biol., 15:675-685, 2020

PubMed Abstract: Thermodynamics and kinetics of protein-ligand binding are both important aspects for the design of novel drug molecules. Presently, thermodynamic data are collected with isothermal titration calorimetry, while kinetic data are mostly derived from surface plasmon resonance. The new method of kinITC provides both thermodynamic and kinetic data from calorimetric titration measurements. The present study demonstrates the convenient collection of calorimetric data suitable for both thermodynamic and kinetic analysis for two series of congeneric ligands of human carbonic anhydrase II and correlates these findings with structural data obtained by macromolecular crystallography to shed light on the importance of shape complementarity for thermodynamics and kinetics governing a protein-ligand binding event. The study shows how minute chemical alterations change preferred ligand conformation and can be used to manipulate thermodynamic and kinetic signatures of binding. They give rise to the observation that analogous -alkyl and -alkyloxy derivatives of identical chain length swap their binding kinetic properties at unchanged binding affinity.

PubMed: 32027480
DOI: 10.1021/acschembio.9b00895

実験手法

X-RAY DIFFRACTION (1.07 Å)