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Although eukaryotic CBS have a similar domain architecture with a catalytic core and a C-terminal Bateman module, their regulation varies widely across phyla. In human CBS (HsCBS), the C-terminus has an autoinhibitory effect by acting as a cap that avoids the entry of substrates into the catalytic site. The binding of the allosteric modulator AdoMet to this region alleviates this cap, allowing the protein to progress from a basal toward an activated state. The same activation is obtained by artificial removal or heat-denaturation of the Bateman module. Recently, we reported the crystal structure of CBS from Toxoplasma gondii (TgCBS) showing that the enzyme assembles into basket-like dimers similar to the basal conformers of HsCBS. These findings would suggest a similar lid function for the Bateman module which, as in HsCBS, should relax in the absence of the C-terminal module. However, herein we demonstrate that, in contrast with HsCBS, removal of the Bateman module in TgCBS through deletion mutagenesis, limited proteolysis, or thermal denaturation has no effects on its activity, oligomerization, and thermal stability. This opposite behavior we have now found in TgCBS provides evidence of a novel type of CBS regulation.<\/jats:p>","DOI":"10.3390\/ijms23158169","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T21:20:59Z","timestamp":1658784059000},"page":"8169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Insights into Domain Organization and Regulatory Mechanism of Cystathionine Beta-Synthase from Toxoplasma gondii"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5999-8667","authenticated-orcid":false,"given":"Carolina","family":"Conter","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry, Department of Biotechnology, University of Verona, Strada le Grazie 15, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4953-8349","authenticated-orcid":false,"given":"Silvia","family":"Fruncillo","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Department of Biotechnology, University of Verona, Strada le Grazie 15, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filippo","family":"Favretto","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Department of Biotechnology, University of Verona, Strada le Grazie 15, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Fern\u00e1ndez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160 Derio, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Dominici","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Department of Biotechnology, University of Verona, Strada le Grazie 15, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5856-9377","authenticated-orcid":false,"given":"Luis Alfonso","family":"Mart\u00ednez-Cruz","sequence":"additional","affiliation":[{"name":"Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160 Derio, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Astegno","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Department of Biotechnology, University of Verona, Strada le Grazie 15, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1096\/fj.02-0211hyp","article-title":"Two\u2019s Company, Three\u2019s A Crowd: Can H2s Be the Third Endogenous Gaseous Transmitter?","volume":"16","author":"Wang","year":"2002","journal-title":"FASEB J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3910","DOI":"10.1093\/emboj\/20.15.3910","article-title":"Structure of Human Cystathionine Beta-Synthase: A Unique Pyridoxal 5\u2032-Phosphate-Dependent Heme Protein","volume":"20","author":"Meier","year":"2001","journal-title":"EMBO J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"20958","DOI":"10.1073\/pnas.1011448107","article-title":"Structural Basis for Substrate Activation and Regulation by Cystathionine Beta-Synthase (Cbs) Domains in Cystathionine \u0392-Synthase","volume":"107","author":"Koutmos","year":"2010","journal-title":"Proc. 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