scholarly journals Evidence against a Direct Interaction between Intracellular Carbonic Anhydrase II and Pure C-terminal Domains of SLC4 Bicarbonate Transporters

2006 ◽  
Vol 282 (2) ◽  
pp. 1409-1421 ◽  
Author(s):  
Peter M. Piermarini ◽  
Eugene Y. Kim ◽  
Walter F. Boron
Keyword(s):  
Carbonic Anhydrase ◽  
Direct Interaction ◽  
Carbonic Anhydrase Ii ◽  
Bicarbonate Transporters ◽  
Terminal Domains

The functional and physical relationship between the DRA bicarbonate transporter and carbonic anhydrase II

2002 ◽  
Vol 283 (5) ◽  
pp. C1522-C1529 ◽  
Author(s):  
Deborah Sterling ◽  
Nathan J. D. Brown ◽  
Claudiu T. Supuran ◽  
Joseph R. Casey
Keyword(s):  
Carbonic Anhydrase ◽  
Direct Interaction ◽  
Carbonic Anhydrase Ii ◽  
Bicarbonate Transport ◽  
Transport Activity ◽  
Physical Relationship ◽  
Hek 293 ◽  
Bicarbonate Transporter ◽  
293 Cells ◽  
Cytoplasmic Tails

COOH-terminal cytoplasmic tails of chloride/bicarbonate anion exchangers (AE) bind cytosolic carbonic anhydrase II (CAII) to form a bicarbonate transport metabolon, a membrane protein complex that accelerates transmembrane bicarbonate flux. To determine whether interaction with CAII affects the downregulated in adenoma (DRA) chloride/bicarbonate exchanger, anion exchange activity of DRA-transfected HEK-293 cells was monitored by following changes in intracellular pH associated with bicarbonate transport. DRA-mediated bicarbonate transport activity of 18 ± 1 mM H+ equivalents/min was inhibited 53 ± 2% by 100 mM of the CAII inhibitor, acetazolamide, but was unaffected by the membrane-impermeant carbonic anhydrase inhibitor, 1-[5-sulfamoyl-1,3,4-thiadiazol-2-yl-(aminosulfonyl-4-phenyl)]-2,6-dimethyl-4-phenyl-pyridinium perchlorate. Compared with AE1, the COOH-terminal tail of DRA interacted weakly with CAII. Overexpression of a functionally inactive CAII mutant, V143Y, reduced AE1 transport activity by 61 ± 4% without effect on DRA transport activity (105 ± 7% transport activity relative to DRA alone). We conclude that cytosolic CAII is required for full DRA-mediated bicarbonate transport. However, DRA differs from other bicarbonate transport proteins because its transport activity is not stimulated by direct interaction with CAII.

scholarly journals Carbonic anhydrase II enhances activity of monocarboxylate transporters via direct interaction

2014 ◽  
Vol 5 ◽  
Author(s):  
Becker Holger ◽  
Heidtmann Hella ◽  
Boone Christopher ◽  
McKenna Robert ◽  
Deitmer Joachim
Keyword(s):  
Carbonic Anhydrase ◽  
Direct Interaction ◽  
Carbonic Anhydrase Ii ◽  
Monocarboxylate Transporters

Inhibition Profiling of Urease and Carbonic Anhydrase II by High- Throughput Screening and Molecular Docking Studies of Structurally Diverse Organic Compounds

2020 ◽  
Vol 17 ◽  
Author(s):  
Majid Ali ◽  
Syed Majid Bukhari ◽  
Asma Zaidi ◽  
Farhan A. Khan ◽  
Umer Rashid ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Carbonic Anhydrase ◽  
Metal Complexes ◽  
Organic Compounds ◽  
High Throughput ◽  
High Throughput Screening ◽  
Docking Studies ◽  
Carbonic Anhydrase Ii ◽  
Molecular Docking Studies ◽  
Ic50 Values

Background:: Structurally diverse organic compounds and available drugs were screened against urease and carbonic anhydrase II in a formulation acceptable for high-throughput screening. Objective: The study was conducted to find out potential inhibitors of urease and carbonic anhydrase II. Methods:: Quantification of the possible HITs was carried out by determining their IC50 values. Results and Discussion:: of several screened compounds including derivatives of oxadiazole, coumarins, chromane-2, 4- diones and metal complexes of cysteine-omeprazole showed promising inhibitory activities with IC50 ranging from 47 μM to 412 μM against the urease. The interactions of active compounds with active sites of enzymes were investigated through molecular docking studies which revealed that (R)-1-(4-amino-4-(5-(thiophen-2-yl)-1,3,4-oxadiazol-2-yl) butyl) guanidine possessing IC50 of 47 μM, interacts with one of the nickel metal atom of urease besides further interactions as predictable hydrogen bonds with KCX490, Asp633, His492, His407 and His409 along with Ala440 and 636. Bi-ligand metal complexes of 4-aminoantipyrine based Schiff bases showed activation of urease with AC50 ranging from 68 μM to 112 μM. Almost 21 compounds with varying functional groups including pyrimidines, oxadiazoles, imidazoles, hydrazides and tin based compounds were active carbonic anhydrase II inhibitors presenting 98 μM to 390 μM IC50 values. Several N-substituted sulfonamide derivatives were inactive against carbonic anhydrase II. Conclusion:: Among all the screened compounds, highly active inhibitor of carbonic anhydrase II was (4-(3- hydroxyphenyl)-6-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl) methanone with IC50 of 98.0 μM. This particular compound showed metallic interaction with Zn ion of carbonic anhydrase II through hydroxyl group of phenyl ring.

Synthesis and Biological Potential Assessment of 2-Substituted Quinazolin-4(3H)-ones as Inhibitors of Phosphodiesterase-I and Carbonic Anhydrase-II

2015 ◽  
Vol 11 (4) ◽  
pp. 336-341 ◽  
Author(s):  
Syed Saad ◽  
Muhammad Saleem ◽  
Shahnaz Perveen ◽  
Muhammad Alam ◽  
Khalid Khan ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Ii ◽  
Biological Potential

Oligodendrocytes express a normal phenotype in carbonic anhydrase II-deficient mice

1989 ◽  
Vol 23 (2) ◽  
pp. 180-190 ◽  
Author(s):  
M. S. Ghandour ◽  
R. P. Skoff ◽  
P. J. Venta ◽  
R. E. Tashian
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Ii ◽  
Normal Phenotype ◽  
Deficient Mice

Chemical Constituents and Carbonic Anhydrase II Activity of Essential Oil of Acridocarpus orientalis A. Juss. in Comparison With Stem and Leaves

2021 ◽  
Vol 24 (1) ◽  
pp. 68-74
Author(s):  
Najeeb Ur Rehman ◽  
Jamal Nasser Alsabahi ◽  
Tanveer Alam ◽  
Ajmal Khan ◽  
Kashif Rafiq ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Essential Oil ◽  
Chemical Constituents ◽  
Carbonic Anhydrase Ii

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.

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