Fluoroalkyl and alkyl chains have similar hydrophobicities in binding to the "hydrophobic wall" of carbonic anhydrase.
نویسندگان
چکیده
The hydrophobic effect, the free-energetically favorable association of nonpolar solutes in water, makes a dominant contribution to binding of many systems of ligands and proteins. The objective of this study was to examine the hydrophobic effect in biomolecular recognition using two chemically different but structurally similar hydrophobic groups, aliphatic hydrocarbons and aliphatic fluorocarbons, and to determine whether the hydrophobicity of the two groups could be distinguished by thermodynamic and biostructural analysis. This paper uses isothermal titration calorimetry (ITC) to examine the thermodynamics of binding of benzenesulfonamides substituted in the para position with alkyl and fluoroalkyl chains (H(2)NSO(2)C(6)H(4)-CONHCH(2)(CX(2))(n)CX(3), n = 0-4, X = H, F) to human carbonic anhydrase II (HCA II). Both alkyl and fluoroalkyl substituents contribute favorably to the enthalpy and the entropy of binding; these contributions increase as the length of chain of the hydrophobic substituent increases. Crystallography of the protein-ligand complexes indicates that the benzenesulfonamide groups of all ligands examined bind with similar geometry, that the tail groups associate with the hydrophobic wall of HCA II (which is made up of the side chains of residues Phe131, Val135, Pro202, and Leu204), and that the structure of the protein is indistinguishable for all but one of the complexes (the longest member of the fluoroalkyl series). Analysis of the thermodynamics of binding as a function of structure is compatible with the hypothesis that hydrophobic binding of both alkyl and fluoroalkyl chains to hydrophobic surface of carbonic anhydrase is due primarily to the release of nonoptimally hydrogen-bonded water molecules that hydrate the binding cavity (including the hydrophobic wall) of HCA II and to the release of water molecules that surround the hydrophobic chain of the ligands. This study defines the balance of enthalpic and entropic contributions to the hydrophobic effect in this representative system of protein and ligand: hydrophobic interactions, here, seem to comprise approximately equal contributions from enthalpy (plausibly from strengthening networks of hydrogen bonds among molecules of water) and entropy (from release of water from configurationally restricted positions).
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 کاملIncreasing binding constants of ligands to carbonic anhydrase by using "greasy tails".
Two series of para-substituted benzenesulfonamides have been examined as inhibitors for bovine carbonic anhydrase II (CAII, EC 4.2.1.1). Both series have hydrophobic alkyl group R connected by amide linkages to the aromatic ring (H2NO2SC6H4-CH2NHCOR1 and H2NO2SC6H4-CONR2R3). The free energy of partitioning (delta Gp) of these ligands between water and octanol had similar, linear correlations wi...
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 کاملBinding Data Analysis for Interaction of n- Alkyl Sulfates with Insulin
The binding data for interaction of a homologous series of n-alkyl sulfates with alkyl chainlengths from C8 to C12 with insulin were analyzed on basis of Hill equation for two classes ofbinding sites .The intrinsic Gibbs free energies were calculated and resolute on basis ofelectrostatic and hydrophobic contributions The estimation of these contributions reveals themajor role of electrostatic i...
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
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of the American Chemical Society
دوره 133 35 شماره
صفحات -
تاریخ انتشار 2011