6I1U

Human Carbonic Anhydrase II in complex with 4-Ethoxybenzenesulfonamide

Summary for 6I1U

• Entry DOI: 10.2210/pdb6i1u/pdb
• Related: 6GDC 6GM9 6HQX 6HR3 6HXD 6I0W
• Descriptor: Carbonic anhydrase 2, ZINC ION, MERCURIBENZOIC ACID, ... (8 entities in total)
• Functional Keywords: lyase, inhibitor, complex, co2 conversion
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 31157.09

Authors

Gloeckner, S.,Heine, A.,Klebe, G. (deposition date: 2018-10-30, release date: 2019-11-20, Last modification date: 2024-01-24)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.08 Å)