The binding of benzoarylsulfonamide ligands to human carbonic anhydrase is insensitive to formal fluorination of the ligand.
نویسندگان
چکیده
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.
منابع مشابه
Study of Glycation Process of Human Carbonic Anhydrase II and Investigation of Effect of Fasting On Enzyme Activity by Using Spectroscopic Methods
Background: Glycation is the non-enzymatic reaction between the carbonyl groups in sugar and free amino groups in proteins. this reaction leads to changes in structure and functions of proteins. Advanced glycation end products (AGEs) is the final stage in this process, which is highly oxidizing and destructive nature, causing many diabetic complications. Methods: In the present investigation, ...
متن کاملThermodynamic parameters for the association of fluorinated benzenesulfonamides with bovine carbonic anhydrase II.
This paper describes a calorimetric study of the association of a series of seven fluorinated benzenesulfonamide ligands (C6H(n)F(5-n)SO2NH2) with bovine carbonic anhydrase II (BCA). Quantitative structure-activity relationships between the free energy, enthalpy, and entropy of binding and pKa and log P of the ligands allowed the evaluation of the thermodynamic parameters in terms of the two in...
متن کاملWater networks contribute to enthalpy/entropy compensation in protein-ligand binding.
The mechanism (or mechanisms) of enthalpy-entropy (H/S) compensation in protein-ligand binding remains controversial, and there are still no predictive models (theoretical or experimental) in which hypotheses of ligand binding can be readily tested. Here we describe a particularly well-defined system of protein and ligands--human carbonic anhydrase (HCA) and a series of benzothiazole sulfonamid...
متن کاملpH Dependence Study of the Kinetic Reaction of Bovine Carbonic Anhydrase with 2,2'-Dithiobispyridine in the Absence and Presence of Surfactants
The pH dependence study reveals that the Cys 206 sulphydryl group of bovine carbonicanhydrase in the native form is not exposed. During the reaction of 2,2'-dithiobispyridine (2-DTP) with the enzyme, there was no absorbance change recorded. In the presence ofsurfactants, the pH dependence profiles of the apparent second order rate constants, kapp, forthe reaction of 2-DTP with bovine carbonic a...
متن کاملGas contaminants capturing by gamma-carbonic anhydrase catalyst: A quantum chemical approach
In this paper, we used quantum chemical approach to shed light on the catalytic mechanism of γ-carbonic anhydrase (γ-CA) to convert carbon dioxide to bicarbonate ion. Density functional theory (DFT) using B3LYP and UB3LYP functional and three split-valance including 6-31G*, 6-311G** and 6-311++G** basis sets were used to calculate the details of electronic structure and electronic energy of act...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Angewandte Chemie
دوره 52 30 شماره
صفحات -
تاریخ انتشار 2013