5JGT

Human carbonic anhydrase II (F131Y/L198A) complexed with 1,3-thiazole-2-sulfonamide

5JGT の概要

• エントリーDOI: 10.2210/pdb5jgt/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, 1,3-thiazole-2-sulfonamide, ... (4 entities in total)
• 機能のキーワード: anhydrase, mutant, water, hydrophobic, lyase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : P00918
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29509.61

構造登録者

Fox, J.M.,Kang, K.,Sastry, M.,Sherman, W.,Sankaran, B.,Zwart, P.H.,Whitesides, G.M. (登録日: 2016-04-20, 公開日: 2017-01-11, 最終更新日: 2023-09-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.1 Å)