Anion inhibition profiles of the γ-carbonic anhydrase from the pathogenic bacterium Burkholderia pseudomallei responsible of melioidosis and highly drug resistant to common antibiotics. Issue 2 (15th January 2017)

• Record Type: Journal Article
• Authors: Del Prete, Sonia; Vullo, Daniela; Di Fonzo, Pietro; Osman, Sameh M.; AlOthman, Zeid; Supuran, Claudiu T.; Capasso, Clemente
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 2(2017)
• Page Start: 575
• Page End: 580
• Publication Date: 2017-01-15
• Subjects: Carbonic anhydrase -- Metalloenzymes -- γ-Class -- Inhibitor -- Anion -- Burkholderia pseudomallei; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.11.021
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Burkholderia pseudomallei is a Gram-negative saprophytic bacterium responsible of melioidosis, an endemic disease of tropical and sub-tropical regions of the world. A recombinant γ-CA (BpsγCA) identified in the genome of this bacterium was cloned and purified. Its catalytic activity and anion inhibition profiles were investigated. The enzyme was an efficient catalyst for the CO2 hydration showing a kcat of 5.3 × 10 5 s −1 and kcat /Km of 2.5 × 10 7 M −1 × s −1 . The best BpsγCA inhibitors were sulfamide, sulfamic acid, phenylboronic acid and phenylarsonic acid, which showed KI in the range of 49–83 μM (these inhibitors showed millimolar inhibition constant against hCA II), followed by diethyldithiocarbamate, selenate, tellurate, perrhenate, selenocyanate, trithiocarbonate, tetraborato, pyrophosphate, stannate, carbonate, bicarbonate, azide, cyanide, thiocyanate and cyanate with KI s in the range of 0.55–9.1 mM. In our laboratories, work is in progress to resolve the X-ray crystal structures of BpsγCA, which may allow the development of small molecule inhibitors with desired properties for targeting and inhibiting specifically the bacterial over the human CAs, considering the fact that B. pseudomallei is involved in a serious bacterial disease.