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CBS possesses a b-type heme coordinated by histidine and cysteine. Fe(III)-CBS is inert toward exogenous ligands, while Fe(II)-CBS is reactive. Both Fe(III)- and Fe(II)-CBS are sensitive to mercury compounds. In this study, we describe the kinetics of the reactions with mercuric chloride (HgCl2) and p-chloromercuribenzoic acid. These reactions were multiphasic and resulted in five-coordinate CBS lacking thiolate ligation, with six-coordinate species as intermediates. Computational QM\/MM studies supported the feasibility of formation of species in which the thiolate is proximal to both the iron ion and the mercury compound. The reactions of Fe(II)-CBS were faster than those of Fe(III)-CBS. The observed rate constants of the first phase increased hyperbolically with concentration of the mercury compounds, with limiting values of 0.3\u20130.4 s\u20131 for Fe(III)-CBS and 40 \u00b1 4 s\u20131 for Fe(II)-CBS. The data were interpreted in terms of alternative models of conformational selection or induced fit. Exposure of Fe(III)-CBS to HgCl2 led to heme release and activity loss. Our study reveals the complexity of the interactions between mercury compounds and CBS.<\/jats:p>","DOI":"10.1021\/acsomega.0c05475","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:01:30Z","timestamp":1610668890000},"page":"2192-2205","source":"Crossref","is-referenced-by-count":5,"title":["Heme-Thiolate Perturbation in Cystathionine \u03b2-Synthase\nby Mercury Compounds"],"prefix":"10.1021","volume":"6","author":[{"given":"Dayana","family":"Benchoam","sequence":"first","affiliation":[{"name":"Universidad de la Repu\u0301blica , , ,","place":["Montevideo, Uruguay, 11400"]},{"name":"Universidad de la Repu\u0301blica , , ,","place":["Montevideo, Uruguay, 11800"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Cuevasanta","sequence":"additional","affiliation":[{"name":"Universidad de la Repu\u0301blica , , ,","place":["Montevideo, Uruguay, 11400"]},{"name":"Universidad de la Repu\u0301blica , , ,","place":["Montevideo, Uruguay, 11800"]},{"name":"Universidad de la Repu\u0301blica , , ,","place":["Montevideo, Uruguay, 11400"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laia","family":"Julio\u0301 Plana","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires\/Instituto de Qui\u0301mica Fi\u0301sica de los Materiales, Medio Ambiente y Energi\u0301a (INQUIMAE-CONICET) , , ,","place":["Buenos Aires, Argentina, C1428EGA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3794-5713","authenticated-orcid":true,"given":"Luciana","family":"Capece","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires\/Instituto de Qui\u0301mica Fi\u0301sica de los Materiales, Medio Ambiente y Energi\u0301a (INQUIMAE-CONICET) , , ,","place":["Buenos Aires, Argentina, C1428EGA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8332-3275","authenticated-orcid":true,"given":"Ruma","family":"Banerjee","sequence":"additional","affiliation":[{"name":"University of Michigan Medical School , , , ,","place":["Ann Arbor, Michigan, United States, 48109"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6911-3132","authenticated-orcid":true,"given":"Beatriz","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Universidad de la Repu\u0301blica , , ,","place":["Montevideo, Uruguay, 11400"]},{"name":"Universidad de la Repu\u0301blica , , ,","place":["Montevideo, Uruguay, 11800"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2021,1,14]]},"reference":[{"key":"2026090209243320700_cit1","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1523\/JNEUROSCI.16-03-01066.1996","article-title":"The possible role of\nhydrogen sulfide as an endogenous\nneuromodulator","volume":"16","author":"Abe","year":"1996","journal-title":"J. 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Food Biochem."},{"key":"2026090209243320700_cit23","doi-asserted-by":"publisher","first-page":"3910","DOI":"10.1093\/emboj\/20.15.3910","article-title":"Structure\nof human cystathionine beta-synthase: a unique pyridoxal 5\u2032-phosphate-dependent\nheme protein","volume":"20","author":"Meier","year":"2001","journal-title":"EMBO J."},{"key":"2026090209243320700_cit24","doi-asserted-by":"publisher","first-page":"10454","DOI":"10.1021\/bi026052d","article-title":"Human cystathionine beta-synthase\nis a heme sensor\nprotein. Evidence that the redox sensor is heme and not the vicinal\ncysteines in the CXXC motif seen in the crystal structure of the truncated\nenzyme","volume":"41","author":"Taoka","year":"2002","journal-title":"Biochemistry"},{"key":"2026090209243320700_cit25","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1515\/irm-2013-0003","article-title":"The redox properties\nof the unique heme in cystathionine \u03b2-synthase","volume":"9","author":"Cuevasanta","year":"2014","journal-title":"BioInorg. React. Mech."},{"key":"2026090209243320700_cit26","doi-asserted-by":"publisher","first-page":"19350","DOI":"10.1074\/jbc.M100029200","article-title":"Pyridoxal phosphate binding sites\nare similar in human\nheme-dependent and yeast heme-independent cystathionine \u03b2-synthases\nEvidence from 31P NMR and pulsed EPR spectroscopy that\nheme and PLP cofactors are not proximal in the human enzyme","volume":"276","author":"Kabil","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2026090209243320700_cit27","doi-asserted-by":"publisher","first-page":"11541","DOI":"10.1074\/jbc.C000056200","article-title":"Yeast cystathionine \u03b2-synthase\nis a pyridoxal phosphate enzyme but, unlike the human enzyme, is not\na heme protein","volume":"275","author":"Jhee","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2026090209243320700_cit28","doi-asserted-by":"publisher","first-page":"6516","DOI":"10.1074\/jbc.M009774200","article-title":"Characterization\nof transsulfuration and cysteine biosynthetic pathways in the protozoan\nhemoflagellate, Trypanosoma cruzi Isolation and molecular\ncharacterization of cystathionine beta-synthase and serine acetyltransferase\nfrom trypanosoma","volume":"276","author":"Nozaki","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2026090209243320700_cit29","doi-asserted-by":"publisher","first-page":"34588","DOI":"10.1074\/jbc.M805928200","article-title":"Active\ncystathionine beta-synthase can be expressed in heme-free systems\nin the presence of metal-substituted porphyrins or a chemical chaperone","volume":"283","author":"Majtan","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2026090209243320700_cit30","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/j.jinorgbio.2009.01.009","article-title":"Modulation of the heme\nelectronic structure and cystathionine beta-synthase activity by second\ncoordination sphere ligands: The role of heme ligand switching in\nredox regulation","volume":"103","author":"Singh","year":"2009","journal-title":"J. Inorg. Biochem."},{"key":"2026090209243320700_cit31","doi-asserted-by":"publisher","first-page":"12809","DOI":"10.1021\/ja904468w","article-title":"Heme regulation\nof human cystathionine beta-synthase activity: Insights from fluorescence\nand Raman spectroscopy","volume":"131","author":"Weeks","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"2026090209243320700_cit32","doi-asserted-by":"publisher","first-page":"6360","DOI":"10.1021\/bi300421z","article-title":"Effect\nof the disease-causing R266K mutation on the heme and PLP environments\nof human cystathionine \u03b2-synthase","volume":"51","author":"Smith","year":"2012","journal-title":"Biochemistry"},{"key":"2026090209243320700_cit33","doi-asserted-by":"publisher","first-page":"37611","DOI":"10.1074\/jbc.M112.414706","article-title":"Allosteric communication between the pyridoxal 5\u2032-phosphate\n(PLP) and heme sites in the H2S generator human cystathionine \u03b2-synthase","volume":"287","author":"Yadav","year":"2012","journal-title":"J. Biol. Chem."},{"key":"2026090209243320700_cit34","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1006\/abbi.1998.0723","article-title":"Trypsin cleavage of human cystathionine\nbeta-synthase into an evolutionarily conserved active core: Structural\nand functional consequences","volume":"355","author":"Kery","year":"1998","journal-title":"Arch. Biochem.\nBiophys."},{"key":"2026090209243320700_cit35","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1107\/S0907444900017893","article-title":"Crystallization\nand preliminary X-ray\ndiffraction analysis of the active core of human recombinant cystathionine\n\u03b2-synthase: An enzyme involved in vascular disease","volume":"57","author":"Janosik","year":"2001","journal-title":"Acta Crystallogr., Sect. D: Biol. 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Inorg.\nBiochem."},{"key":"2026090209243320700_cit39","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.abb.2009.08.022","article-title":"Inactivation\nof cystathionine beta-synthase with peroxynitrite","volume":"491","author":"Celano","year":"2009","journal-title":"Arch. Biochem. Biophys."},{"key":"2026090209243320700_cit40","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1006\/bbrc.2001.4807","article-title":"Coordination chemistry of the heme in cystathionine\nbeta-synthase: formation of iron(ii)-isonitrile complexes","volume":"283","author":"Vadon-Le Goff","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2026090209243320700_cit41","doi-asserted-by":"publisher","first-page":"8579","DOI":"10.1074\/jbc.M113.507533","article-title":"NO* binds human cystathionine \u03b2-synthase quickly\nand tightly","volume":"289","author":"Vicente","year":"2014","journal-title":"J. Biol. 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Biol. Chem."},{"key":"2026090209243320700_cit46","doi-asserted-by":"publisher","first-page":"2738","DOI":"10.1021\/bi9826052","article-title":"Characterization of the heme and\npyridoxal phosphate cofactors of human cystathionine beta-synthase\nreveals nonequivalent active sites","volume":"38","author":"Taoka","year":"1999","journal-title":"Biochemistry"},{"key":"2026090209243320700_cit47","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/S0162-0134(01)00335-X","article-title":"Characterization of NO binding to human cystathionine\nbeta-synthase: Possible implications of the effects of CO and NO binding\nto the human enzyme","volume":"87","author":"Taoka","year":"2001","journal-title":"J. Inorg. Biochem."},{"key":"2026090209243320700_cit48","doi-asserted-by":"crossref","unstructured":"Carballal, S.; Cuevasanta, E.; Yadav, P. K.; Gherasim, C.; Ballou, D. 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