Kinetic and spectroscopic studies of hydrophilic amino acid substitutions in the hydrophobic pocket of human carbonic anhydrase II

Biochemistry ◽  
1993 ◽  
Vol 32 (17) ◽  
pp. 4496-4505 ◽  
Author(s):  
Joseph F. Krebs ◽  
Fazale Rana ◽  
Richard A. Dluhy ◽  
Carol A. Fierke
Keyword(s):  
Amino Acid ◽  
Carbonic Anhydrase ◽  
Spectroscopic Studies ◽  
Carbonic Anhydrase Ii ◽  
Amino Acid Substitutions ◽  
Hydrophobic Pocket ◽  
Hydrophilic Amino Acid ◽  
Human Carbonic Anhydrase

scholarly journals Importance of C-Terminal Knot Structure in Carbonic Anhydrase II (Part I): Role of C-Terminal Knot Forming GLN253 on Enzymatic Property of Human Carbinic II

1970 ◽  
Vol 14 ◽  
pp. 1-9
Author(s):  
Mohammad Taufiq Alam
Keyword(s):  
Amino Acid ◽  
Carbonic Anhydrase ◽  
Point Mutation ◽  
Amino Acid Residue ◽  
Active Site ◽  
Terminal Region ◽  
Carbonic Anhydrase Ii ◽  
C Terminus ◽  
Human Carbonic Anhydrase

In both, bovine and human carbonic anhydrase II, a conserved glutamine residue occupies the position in the middle of the knot, which is formed by intercrossing of C-terminal end with N-terminal region. Previous studies have indicated that C-terminus is not the part of an active site, but truncation of 7 amino acid residue in this region can have marked effects on stability of the enzyme (data not published). To gain further insight into the role of specific amino acid residue in C-terminal region, site directed mutagenesis was used to introduce point mutation. Substitution of glutamine with cysteine was chosen because the cysteine residue is less hydrophilic as compared with glutamine and thus, may disrupt the hydrophilic environment in this region. Result indicates that Gln253 located within the C-terminus knot topology plays a significant role in normal function of the enzyme. Thus, C-terminal region might mediate cooperativity between the central active site of the enzyme through proper formation of knot. Key words: Human carbonic anhydrase II; knot topology; point mutation J. bio-sci. 14: 1-9, 2006

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.

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