{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:07:48Z","timestamp":1787004468022,"version":"build-2736575974"},"reference-count":53,"publisher":"Portland Press Ltd.","issue":"6","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,3,15]]},"abstract":"<jats:p>Toxoplasma gondii is a protozoan parasite of medical and veterinary relevance responsible for toxoplasmosis in humans. As an efficacious vaccine remains a challenge, chemotherapy is still the most effective way to combat the disease. In search of novel druggable targets, we performed a thorough characterization of the putative pyridoxal 5\u2032-phosphate (PLP)-dependent enzyme ornithine aminotransferase from T. gondii ME49 (TgOAT). We overexpressed the protein in Escherichia coli and analysed its molecular and kinetic properties by UV-visible absorbance, fluorescence and CD spectroscopy, in addition to kinetic studies of both the steady state and pre-steady state. TgOAT is largely similar to OATs from other species regarding its general transamination mechanism and spectral properties of PLP; however, it does not show a specific ornithine aminotransferase activity like its human homologue, but exhibits both N-acetylornithine and \u03b3-aminobutyric acid (GABA) transaminase activity in vitro, suggesting a role in both arginine and GABA metabolism in vivo. The presence of Val79 in the active site of TgOAT in place of Tyr, as in its human counterpart, provides the necessary room to accommodate N-acetylornithine and GABA, resembling the active site arrangement of GABA transaminases. Moreover, mutation of Val79 to Tyr results in a change of substrate preference between GABA, N-acetylornithine and L-ornithine, suggesting a key role of Val79 in defining substrate specificity. The findings that TgOAT possesses parasite-specific structural features as well as differing substrate specificity from its human homologue make it an attractive target for anti-toxoplasmosis inhibitor design that can be exploited for chemotherapeutic intervention.<\/jats:p>","DOI":"10.1042\/bcj20161021","type":"journal-article","created":{"date-parts":[[2017,1,26]],"date-time":"2017-01-26T20:10:57Z","timestamp":1485461457000},"page":"939-955","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Unique substrate specificity of ornithine aminotransferase from\n                    <i>Toxoplasma gondii<\/i>"],"prefix":"10.1042","volume":"474","author":[{"given":"Alessandra","family":"Astegno","sequence":"first","affiliation":[{"name":"Department of Biotechnology, University of Verona, Verona 37134, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Maresi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, University of Verona, Verona 37134, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariarita","family":"Bertoldi","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona 37134, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"La Verde","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, University of Verona, Verona 37134, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Paiardini","sequence":"additional","affiliation":[{"name":"Dipartimento di Biologia e Biotecnologie \u2018Charles Darwin\u2019, Sapienza Universit\u00e0 di Roma, Piazzale Aldo Moro 5, Rome 00185, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Dominici","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, University of Verona, Verona 37134, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2017,3,7]]},"reference":[{"key":"2021112216461961500_BCJ-2016-1021C1","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.1016\/s0140-6736(04)16412-x","article-title":"Toxoplasmosis","volume":"363","author":"Montoya","year":"2004","journal-title":"Lancet"},{"key":"2021112216461961500_BCJ-2016-1021C2","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/S0146-0005(98)80022-0","article-title":"Toxoplasmosis","volume":"22","author":"Beazley","year":"1998","journal-title":"Semin. 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