These authors contributed equally to this work.
The Binding of Benzoarylsulfonamide Ligands to Human Carbonic Anhydrase is Insensitive to Formal Fluorination of the Ligand†
Article first published online: 20 JUN 2013
Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angewandte Chemie International Edition
Volume 52, Issue 30, pages 7714–7717, July 22, 2013
How to Cite
Lockett, M. R., Lange, H., Breiten, B., Heroux, A., Sherman, W., Rappoport, D., Yau, P. O., Snyder, P. W. and Whitesides, G. M. (2013), The Binding of Benzoarylsulfonamide Ligands to Human Carbonic Anhydrase is Insensitive to Formal Fluorination of the Ligand . Angew. Chem. Int. Ed., 52: 7714–7717. doi: 10.1002/anie.201301813
The authors thank Dr. Jasmin Mecinovic, Dr. Ramani Ranatunge, Dr. Demetri Moustakas, Dr. Manza Atkinson, Dr. Mohammad Al-Sayah, Dr. Shuji Fujita, and Mr. Jang Hoon Yoon for their technical contributions. This work was supported by the National Science Foundation (CHE-1152196) and the Wyss Institute of Biologically Inspired Engineering. H.L. thanks the Deutsche Forschungsgemeinschaft (DFG) for a postdoctoral stipend.
- Issue published online: 17 JUL 2013
- Article first published online: 20 JUN 2013
- Manuscript Revised: 10 MAY 2013
- Manuscript Received: 3 MAR 2013
- National Science Foundation. Grant Number: CHE-1152196
- Wyss Institute of Biologically Inspired Engineering
- Deutsche Forschungsgemeinschaft (DFG)
- biomolecular recognition;
- carbonic anhydrase;
- hydrophobic effect;
- protein-ligand binding;
It's the water that matters. Pairs of benzo- and perfluorobenzoarylsulfonamide ligands bind to human carbonic anhydrase with a conserved binding geometry, an enthalpy-driven binding, and indistinguishable binding affinities (see picture). These data support the pervasive theory that the lock-and-key model disregards an important component of binding: the water, which fills the binding pocket of the protein and surrounds the ligand.