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Öğe Cloning, expression and biochemical characterization of a beta-carbonic anhydrase from the soil bacterium Enterobacter sp B13(TAYLOR & FRANCIS LTD, 2016) Eminoglu, Aysenur; Vullo, Daniela; Asik, Aycan; Colak, Dilsat Nigar; Supuran, Claudiu T.; Canakci, Sabriye; Belduz, Ali OsmanA recombinant carbonic anhydrase (CA, EC 4.2.1.1) from the soil-dwelling bacterium Enterobacter sp. B13 was cloned and purified by Co2+ affinity chromatography. Bioinformatic analysis showed that the new enzyme (denominated here B13-CA) belongs to the beta-class CAs and to possess 95% homology with the ortholog enzyme from Escherichia coli encoded by the can gene, whereas its sequence homology with the other such enzyme from E. coli (encoded by the cynT gene) was of 33%. B13-CA was characterized kinetically as a catalyst for carbon dioxide hydration to bicarbonate and protons. The enzyme shows a significant catalytic activity, with the following kinetic parameters at 20 degrees C and pH of 8.3: k(cat) of 4.8 x 10(5) s(-1) and k(cat)/K-m of 5.6 x 10(7) M-1 x s(-1). This activity was potently inhibited by acetazolamide which showed a K-l of 78.9 nM. Although only this compound was investigated for the moment as B13-CA inhibitor, further studies may reveal new classes of inhibitors/activators of this enzyme which may show biomedical or environmental applications, considering the posssible role of this enzyme in CaCO3 biomineralization processes.Öğe Investigation of inhibitory properties of some hydrazone compounds on hCA I, hCA II and AChE enzymes(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2019) Kucukoglu, Kaan; Gul, Halise Inci; Taslimi, Parham; Gulcin, Ilhami; Supuran, Claudiu T.Recently, inhibition of carbonic anhydrase (hCA) and acetylcholinesterase (AChE) have appeared as a promising approach for pharmacological intervention in a variety of disorders such as glaucoma, epilepsy, obesity, cancer, and Alzheimer's disease. Keeping this in mind, N, N'-bis[(1-aryl-3-heteroaryl) propylidene] hydrazine dihydrochlorides, N1-N11, P1, P4-P8, and R1-R6, were synthesized to investigate their inhibitory activity against hCA I, hCA II, and AChE enzymes. All compounds in N, P, and R-series inhibited hCAs (I and II) and AChE more efficiently than the reference compounds acetazolamide (AZA), and tacrine. According to the activity results, the most effective inhibitory compounds were in R-series with the K-i values of 203 +/- 55-473 +/- 67 nM and 200 +/- 34-419 +/- 94 nM on hCA I, and hCA II, respectively. N, N'-Bis[1-(4-fluorophenyl)-3-(morpholine-4-yl) propylidene] hydrazine dihydrochlorides, N8, in N-series, N, N'-Bis[1-(4-hydroxyphenyl)-3-(piperidine-1-yl) pro-pylidene] hydrazine dihydrochlorides, P4, in P-series, and N, N'-bis[1-(4-chlorophenyl)-3-(pyrrolidine-1-yl) pro-pylidene] hydrazine dihydrochlorides, R5, in R-series were the most powerful compounds against hCA I with the K-i values of 438 +/- 65 nM, 344 +/- 64 nM, and 203 +/- 55 nM, respectively. Similarly, N8, P4, and R5 efficiently inhibited hCA II isoenzyme with the K-i values of 405 +/- 60 nM, 327 +/- 80 nM, and 200 +/- 34 nM, respectively. On the other hand, P-series compounds had notable inhibitory effect against AChE than the reference compound tacrine and the K-i values were between 66 +/- 20 nM and 128 +/- 36 nM. N, N'-Bis[1-(4-fluorophenyl)-3-(piperidine-1-yl) propylidene] hydrazine dihydrochlorides, P7, was the most potent compound on AChE with the K-i value of 66 +/- 20 nM. The other most promising compounds, N, N'-bis[1-(4-hydroxyphenyl)-3-(morpholine-4-yl) propylidene] hydrazine dihydrochlorides, N4 in N-series and N, N'-bis[1-(4-hydroxyphenyl)-3-(pyrrolidine-1-yl) propylidene] hydrazine dihydrochlorides, R4 in R-series were againts AChE with the K-i values of 119 +/- 20 nM, 88 +/- 14 nM, respectively.Öğe Sulfonamide inhibition studies of the beta-carbonic anhydrase from the newly discovered bacterium Enterobacter sp B13(PERGAMON-ELSEVIER SCIENCE LTD, 2016) Eminoglu, Aysenur; Vullo, Daniela; Asik, Aycan; Colak, Dilsat Nigar; Canakci, Sabriye; Belduz, Ali Osman; Supuran, Claudiu T.The genome of the newly identified bacterium Enterobacter sp. B13 encodes for a beta-class carbonic anhydrases (CAs, EC 4.2.1.1), EspCA. This enzyme was recently cloned, and characterized kinetically by this group (J. Enzyme Inhib. Med. Chem. 2016, 31). Here we report an inhibition study with sulfonamides and sulfamates of this enzyme. The best EspCA inhibitors were some sulfanylated sulfonamides with elongated molecules, metanilamide, 4-aminoalkyl-benzenesulfonamides, acetazolamide, and deacetylated methazolamide (K(I)s in the range of 58.7-96.5 nM). Clinically used agents such as methazolamide, ethoxzolamide, dorzolamide, brinzolamide, benzolamide, zonisamide, sulthiame, sulpiride, topiramate and valdecoxib were slightly less effective inhibitors (K(I)s in the range of 103-138 nM). Saccharin, celecoxib, dichlorophenamide and many simple benzenesulfonamides were even less effective as EspCA inhibitors, with K(I)s in the range of 384-938 nM. Identification of effective inhibitors of this bacterial enzyme may lead to pharmacological tools useful for understanding the physiological role(s) of the beta-class CAs in bacterial pathogenicity/virulence. (C) 2016 Elsevier Ltd. All rights reserved.