scholarly journals A Kinetic Model of the Monocarboxylate Transporter MCT1 and its Interaction with Carbonic Anhydrase II

2010 ◽  
Vol 03 (05) ◽  
Author(s):  
Almquist J
Keyword(s):  
Kinetic Model ◽  
Carbonic Anhydrase ◽  
Monocarboxylate Transporter ◽  
Carbonic Anhydrase Ii

scholarly journals A surface proton antenna in carbonic anhydrase II supports lactate transport in cancer cells

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sina Ibne Noor ◽  
Somayeh Jamali ◽  
Samantha Ames ◽  
Silke Langer ◽  
Joachim W Deitmer ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Xenopus Oocytes ◽  
Proton Exchange ◽  
Monocarboxylate Transporter ◽  
Carbonic Anhydrase Ii ◽  
Transport Activity ◽  
Proton Shuttling ◽  
Mcf 7

Many tumor cells produce vast amounts of lactate and acid, which have to be removed from the cell to prevent intracellular lactacidosis and suffocation of metabolism. In the present study, we show that proton-driven lactate flux is enhanced by the intracellular carbonic anhydrase CAII, which is colocalized with the monocarboxylate transporter MCT1 in MCF-7 breast cancer cells. Co-expression of MCTs with various CAII mutants in Xenopus oocytes demonstrated that CAII facilitates MCT transport activity in a process involving CAII-Glu69 and CAII-Asp72, which could function as surface proton antennae for the enzyme. CAII-Glu69 and CAII-Asp72 seem to mediate proton transfer between enzyme and transporter, but CAII-His64, the central residue of the enzyme’s intramolecular proton shuttle, is not involved in proton shuttling between the two proteins. Instead, this residue mediates binding between MCT and CAII. Taken together, the results suggest that CAII features a moiety that exclusively mediates proton exchange with the MCT to facilitate transport activity.

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
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