5JEG

Human carbonic anhydrase II (V121I) complexed with benzo[d]thiazole-2-sulfonamide

Summary for 5JEG

• Entry DOI: 10.2210/pdb5jeg/pdb
• Related: 5JDV 5JE7 5JEH 5JEP 5JES 5JG3 5JG5
• Descriptor: Carbonic anhydrase 2, ZINC ION, 1,3-benzothiazole-2-sulfonamide, ... (4 entities in total)
• Functional Keywords: anhydrase, mutant, hydrophobic, lyase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 29649.83

Authors

Fox, J.M.,Kang, K.,Sastry, M.,Sherman, W.,Sankaran, B.,Zwart, P.H.,Whitesides, G.M. (deposition date: 2016-04-18, release date: 2017-01-11, Last modification date: 2024-03-06)

Primary citation

Fox, J.M.,Kang, K.,Sastry, M.,Sherman, W.,Sankaran, B.,Zwart, P.H.,Whitesides, G.M.
Water-Restructuring Mutations Can Reverse the Thermodynamic Signature of Ligand Binding to Human Carbonic Anhydrase.
Angew. Chem. Int. Ed. Engl., 56:3833-3837, 2017

PubMed Abstract: This study uses mutants of human carbonic anhydrase (HCAII) to examine how changes in the organization of water within a binding pocket can alter the thermodynamics of protein-ligand association. Results from calorimetric, crystallographic, and theoretical analyses suggest that most mutations strengthen networks of water-mediated hydrogen bonds and reduce binding affinity by increasing the enthalpic cost and, to a lesser extent, the entropic benefit of rearranging those networks during binding. The organization of water within a binding pocket can thus determine whether the hydrophobic interactions in which it engages are enthalpy-driven or entropy-driven. Our findings highlight a possible asymmetry in protein-ligand association by suggesting that, within the confines of the binding pocket of HCAII, binding events associated with enthalpically favorable rearrangements of water are stronger than those associated with entropically favorable ones.

PubMed: 28252841
DOI: 10.1002/anie.201609409

Experimental method

X-RAY DIFFRACTION (1.19 Å)