{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:30:37Z","timestamp":1790505037158,"version":"4.1.0"},"reference-count":83,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2017,3,7]],"date-time":"2017-03-07T00:00:00Z","timestamp":1488844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP160102681"],"award-info":[{"award-number":["DP160102681"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>We have cloned, purified, and characterized a \u03b2-carbonic anhydrase (CA, EC 4.2.1.1), BpsCA\u03b2, from the pathogenic bacterium Burkholderia pseudomallei, responsible for the tropical disease melioidosis. The enzyme showed high catalytic activity for the physiologic CO2 hydration reaction to bicarbonate and protons, with the following kinetic parameters: kcat of 1.6 \u00d7 105 s\u22121 and kcat\/KM of 3.4 \u00d7 107 M\u22121 s\u22121. An inhibition study with a panel of 38 sulfonamides and one sulfamate\u2014including 15 compounds that are used clinically\u2014revealed an interesting structure\u2013activity relationship for the interaction of this enzyme with these inhibitors. Many simple sulfonamides and clinically used agents such as topiramate, sulpiride, celecoxib, valdecoxib, and sulthiame were ineffective BpsCA\u03b2 inhibitors (KI &gt; 50 \u00b5M). Other drugs, such as ethoxzolamide, dorzolamide, brinzolamide, zonisamide, indisulam, and hydrochlorothiazide were moderately potent micromolar inhibitors. The best inhibition was observed with benzene-1,3-disulfonamides\u2014benzolamide and its analogs acetazolamide and methazolamide\u2014which showed KI in the range of 185\u2013745 nM. The inhibition profile of BpsCA\u03b2 is very different from that of the \u03b3-class enzyme from the same pathogen, BpsCA\u03b3. Thus, identifying compounds that would effectively interact with both enzymes is relatively challenging. However, benzolamide was one of the best inhibitors of both of these CAs with KI of 653 and 185 nM, respectively, making it an interesting lead compound for the design of more effective agents, which may be useful tools for understanding the pathogenicity of this bacterium.<\/jats:p>","DOI":"10.3390\/molecules22030421","type":"journal-article","created":{"date-parts":[[2017,3,7]],"date-time":"2017-03-07T11:12:32Z","timestamp":1488885152000},"page":"421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Comparison of the Sulfonamide Inhibition Profiles of the \u03b2- and \u03b3-Carbonic Anhydrases from the Pathogenic Bacterium Burkholderia pseudomallei"],"prefix":"10.3390","volume":"22","author":[{"given":"Daniela","family":"Vullo","sequence":"first","affiliation":[{"name":"Laboratorio di Chimica Bioinorganica, Dipartimento Di Chimica, Universit\u00e0 degli Studi di Firenze, Polo Scientifico, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Del Prete","sequence":"additional","affiliation":[{"name":"Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 111, 80131 Napoli, Italy"},{"name":"Sezione di Scienze Farmaceutiche e Nutraceutiche, Dipartimento Neurofarba, Universit\u00e0 degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Di Fonzo","sequence":"additional","affiliation":[{"name":"Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 111, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Carginale","sequence":"additional","affiliation":[{"name":"Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 111, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Donald","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of New South Wales, Sydney, New South Wales 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4262-0323","authenticated-orcid":false,"given":"Claudiu","family":"Supuran","sequence":"additional","affiliation":[{"name":"Sezione di Scienze Farmaceutiche e Nutraceutiche, Dipartimento Neurofarba, Universit\u00e0 degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy"},{"name":"School of Chemistry, University of New South Wales, Sydney, New South Wales 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3314-2411","authenticated-orcid":false,"given":"Clemente","family":"Capasso","sequence":"additional","affiliation":[{"name":"Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 111, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.bmcl.2016.11.027","article-title":"Burkholderia pseudomallei \u03b3-carbonic anhydrase is strongly activated by amino acids and amines","volume":"27","author":"Vullo","year":"2017","journal-title":"Bioorg. Med. Chem. 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