Sulfonamide inhibition profile of the γ-carbonic anhydrase identified in the genome of the pathogenic bacterium Burkholderia pseudomallei the etiological agent responsible of melioidosis

Comparison of the Sulfonamide Inhibition Profiles of the β- and γ-Carbonic Anhydrases from the Pathogenic Bacterium Burkholderia pseudomallei

“…In Table 2 are shown the rate constants (k cat , K M , and k cat /K M ) of the BpsCAβ identified in the genome of Burkholderia pseudomallei and the inhibition constant (K I ) using the inhibitor acetazolamide. These constants were compared with the kinetic parameters of the α-CA from the Homo sapiens (isoforms hCA I and hCA II) and with those obtained from BpsCAγ that were reported previously [ 7 ]. The catalytic activity values of these enzymes were determined using the “stopped-flow” technique.…”

“…(iv) The inhibition profile of BpsCAβ differs substantially from that of the γ-class enzyme from the same pathogen (BpsCAγ) that was recently investigated by this group [ 7 ]. A relatively limited number of sulfonamides that have been investigated act as effective CAIs against both the β- and γ-CAs from this bacterium ( Table 3 ).…”

“…CAs are ubiquitous metalloenzymes that catalyze the reversible hydration of carbon dioxide with the production of bicarbonate and protons. The CA superfamily includes seven distinct classes known as the α, β, γ, δ, ζ, η, and θ [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. The α-, β-, δ-, η-, and perhaps θ-CAs use Zn(II) ions at the active site, the γ-CAs are probably Fe(II) enzymes (but they are also active with bound Zn(II) or Co(II) ions) [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ], and the ζ-class CAs are cambialistic enzymes, active both with Cd(II) or Zn(II) bound within the active site in order to perform the physiologic reaction catalysis [ 22 , 23 , 24 ].…”

“…In the present manuscript, the inhibition profile of BpsCAβ was investigated using a wide series of sulfonamides/sulfamates. The inhibition profile of BpsCAβ was compared with those obtained for the human α-CAs (hCA I and hCAII) and the other bacterial BpsCAγ previously identified in the genome of Burkholderia pseudomallei [ 7 ] and investigated by our groups for its inhibition profiles with anions and sulfonamides. This study may be of interest for designing new types of inhibitors that may have clinical applications, because Burkholderia pseudomallei is fundamentally resistant to penicillin, ampicillin, first-generation and second-generation cephalosporins, macrolides, quinolones, and most aminoglycosides [ 48 ].…”

Crystal Structure of a Tetrameric Type II β-Carbonic Anhydrase from the Pathogenic Bacterium Burkholderia pseudomallei

“…This feature is of great interest, because these three classes are not expressed in humans, giving the opportunity to inhibit these classes preferentially. Our group recently reported the catalytic activity and the sulfonamide and anion inhibition profiles of the recombinant βand γ-CAs from B. pseudomallei, named BpsβCA and BpsγCA, respectively [21][22][23]. In the last ten years, numerous results concerning the inhibition profile of the three bacterial CA classes (α, β, and γ) were reported using anions and sulfonamides.…”