Nitrogen-15 NMR studies of the complex of carbonic anhydrase with the novel carbonyl hydration substrate pyruvamide. Evidence for the coordination of the deprotonated amide group to the active site zinc

1987 ◽  
Vol 109 (23) ◽  
pp. 7232-7233 ◽  
Author(s):  
Jogeshwar Mukherjee ◽  
Janice I. Rogers ◽  
Raja G. Khalifah ◽  
Grover W. Everett
Keyword(s):  
Carbonic Anhydrase ◽  
Active Site ◽  
Amide Group ◽  
The Novel ◽  
Nmr Studies

NMR Studies of Active-Site Properties of Human Carbonic Anhydrase II by Using15N-Labeled 4-Methylimidazole as a Local Probe and Histidine Hydrogen-Bond Correlations

2014 ◽  
Vol 21 (7) ◽  
pp. 2915-2929 ◽  
Author(s):  
Ilya G. Shenderovich ◽  
Stepan B. Lesnichin ◽  
Chingkuang Tu ◽  
David N. Silverman ◽  
Peter M. Tolstoy ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Carbonic Anhydrase ◽  
Active Site ◽  
Carbonic Anhydrase Ii ◽  
Nmr Studies ◽  
Human Carbonic Anhydrase

scholarly journals Probing the ionization state of substrate α-d-glucopyranosyl phosphate bound to glycogen phosphorylase b

1995 ◽  
Vol 308 (3) ◽  
pp. 1017-1023 ◽  
Author(s):  
I P Street ◽  
S G Withers
Keyword(s):  
Active Site ◽  
Glycogen Phosphorylase ◽  
Ph Dependence ◽  
Substrate Inhibition ◽  
19F Nmr ◽  
Ionization State ◽  
Nmr Studies ◽  
Substrate Analogues ◽  
Glycogen Phosphorylase B ◽  
Pka Value

The ionization state of the substrate alpha-D-glucopyranosyl phosphate bound at the active site of glycogen phosphorylase has been probed by a number of techniques. Values of Ki determined for a series of substrate analogue inhibitors in which the phosphate moiety bears differing charges suggest that the enzyme will bind both the monoanionic and dianionic substrates with approximately equal affinity. These results are strongly supported by 31P- and 19F-NMR studies of the bound substrate analogues alpha-D-glucopyranosyl 1-methylenephosphonate and 2-deoxy-2-fluoro-alpha-D-glucopyranosyl phosphate, which also suggest that the substrate can be bound in either ionization state. The pH-dependences of the inhibition constants K1 for these two analogues, which have substantially different phosphate pK2 values (7.3 and 5.9 respectively), are found to be essentially identical with the pH-dependence of K(m) values for the substrate, inhibition decreasing according to an apparent pKa value of 7.2. This again indicates that there is no specificity for monoanion or dianion binding and also reveals that binding is associated with the uptake of a proton. As the bound substrate is not protonated, this proton must be taken up by the proton.

scholarly journals The Influence of Varying Fluorination Patterns on the Thermodynamics and Kinetics of Benzenesulfonamide Binding to Human Carbonic Anhydrase II

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 509 ◽  
Author(s):  
Steffen Glöckner ◽  
Khang Ngo ◽  
Björn Wagner ◽  
Andreas Heine ◽  
Gerhard Klebe
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Ii ◽  
The Novel ◽  
Binding Modes ◽  
X Ray ◽  
Structure Activity ◽  
Small Set ◽  
Novel Method ◽  
Human Carbonic Anhydrase ◽  
Kinetics Of

The fluorination of lead-like compounds is a common tool in medicinal chemistry to alter molecular properties in various ways and with different goals. We herein present a detailed study of the binding of fluorinated benzenesulfonamides to human Carbonic Anhydrase II by complementing macromolecular X-ray crystallographic observations with thermodynamic and kinetic data collected with the novel method of kinITC. Our findings comprise so far unknown alternative binding modes in the crystalline state for some of the investigated compounds as well as complex thermodynamic and kinetic structure-activity relationships. They suggest that fluorination of the benzenesulfonamide core is especially advantageous in one position with respect to the kinetic signatures of binding and that a higher degree of fluorination does not necessarily provide for a higher affinity or more favorable kinetic binding profiles. Lastly, we propose a relationship between the kinetics of binding and ligand acidity based on a small set of compounds with similar substitution patterns.

Active-site engineering of carbonic anhydrase and its application to biosensors

2000 ◽  
pp. 221-240 ◽  
Author(s):  
Jennifer A. Hunt ◽  
Charles A. Lesburg ◽  
David W. Christianson ◽  
Richard B. Thompson ◽  
Carol A. Fierke
Keyword(s):  
Carbonic Anhydrase ◽  
Active Site
Sign in / Sign up

Export Citation Format

Share Document