Protein Surface-Assisted Enhancement in the Binding Affinity of an Inhibitor for Recombinant Human Carbonic Anhydrase-II

2004 ◽  
Vol 126 (35) ◽  
pp. 10875-10883 ◽  
Author(s):  
Abir L. Banerjee ◽  
Michael Swanson ◽  
Bidhan C. Roy ◽  
Xiao Jia ◽  
Manas K. Haldar ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Binding Affinity ◽  
Carbonic Anhydrase Ii ◽  
Protein Surface ◽  
Human Carbonic Anhydrase

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.

Salt mediated unusual switching in the aggregation kinetic profile of human carbonic anhydrase

RSC Advances ◽  
2015 ◽  
Vol 5 (116) ◽  
pp. 95717-95726 ◽  
Author(s):  
Preeti Gupta ◽  
Shashank Deep
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Ii ◽  
Aggregation Kinetic ◽  
Kinetic Profile ◽  
Human Carbonic Anhydrase

Aggregation pathway of human carbonic anhydrase II in the presence of salt.

Electron spin echo decay as a probe of aminoxyl environment in spin-labeled mutants of human carbonic anhydrase II †

1997 ◽  
pp. 2549-2554 ◽  
Author(s):  
Mikael Lindgren ◽  
Gareth R. Eaton ◽  
Sandra S. Eaton ◽  
Bengt-Harald Jonsson ◽  
Per Hammarström ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Electron Spin ◽  
Spin Echo ◽  
Electron Spin Echo ◽  
Carbonic Anhydrase Ii ◽  
Human Carbonic Anhydrase

scholarly journals Structure of a monoclinic polymorph of human carbonic anhydrase II with a doubledaaxis

2010 ◽  
Vol 66 (5) ◽  
pp. 628-634 ◽  
Author(s):  
Arthur H. Robbins ◽  
John F. Domsic ◽  
Mavis Agbandje-McKenna ◽  
Robert McKenna
Keyword(s):  
Carbonic Anhydrase ◽  
Crystal Packing ◽  
Rotation Axis ◽  
Unit Cell ◽  
Carbonic Anhydrase Ii ◽  
Monoclinic Unit Cell ◽  
Structure Solution ◽  
Unit Cells ◽  
Human Carbonic Anhydrase ◽  
Β Sheet

The crystal structure of human carbonic anhydrase II with a doubledaaxis from that of the usually observed monoclinic unit cell has been determined and refined to 1.4 Å resolution. The diffraction data withh= 2n+ 1 were systematically weaker than those withh= 2n. Consequently, the scaling of the data, structure solution and refinement were challenging. The two molecules comprising the asymmetric unit are related by a noncrystallographic translation of ½ alonga, but one of the molecules has two alternate positions related by a rotation of approximately 2°. This rotation axis is located near the edge of the central β-sheet, causing a maximum distance disparity of 1.7 Å between equivalent atoms on the diametrically opposite side of the molecule. The crystal-packing contacts are similar to two sequential combined unit cells alongaof the previously determined monoclinic unit cell. Abnormally high finalRcrystandRfreevalues (20.2% and 23.7%, respectively) are not unusual for structures containing pseudo-translational symmetry and probably result from poor signal to noise in the weakh-odd data.

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