{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":44,"searchCount":0},"additional":{"submitter":["Benchoam D"],"funding":["Comisi?n Acad?mica de Posgrado, Universidad de la Rep?blica, Uruguay","Comisi?n Sectorial de Investigaci?n Cient?fic, Universidad de la Rep?blica, Uruguay","National Heart, Lung, and Blood Institute","NHLBI NIH HHS","Ministerio de Educaci?n y Cultura - Universidad de la Rep?blica, Uruguay","NIGMS NIH HHS"],"pagination":["2192-2205"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7841933"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6(3)"],"pubmed_abstract":["Cystathionine β-synthase (CBS) is an enzyme involved in sulfur metabolism that catalyzes the pyridoxal phosphate-dependent condensation of homocysteine with serine or cysteine to form cystathionine and water or hydrogen sulfide (H<sub>2</sub>S), respectively. CBS possesses a <i>b</i>-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 (HgCl<sub>2</sub>) and <i>p</i>-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 0.3-0.4 s<sup>-1</sup> for Fe(III)-CBS and 40 ± 4 s<sup>-1</sup> 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 HgCl<sub>2</sub> led to heme release and activity loss. Our study reveals the complexity of the interactions between mercury compounds and CBS."],"journal":["ACS omega"],"pubmed_title":["Heme-Thiolate Perturbation in Cystathionine β-Synthase by Mercury Compounds."],"pmcid":["PMC7841933"],"funding_grant_id":["R01 HL058984","HL58984","R35 GM130183"],"pubmed_authors":["Banerjee R","Benchoam D","Cuevasanta E","Capece L","Alvarez B","Julio Plana L"],"view_count":["44"],"additional_accession":[]},"is_claimable":false,"name":"Heme-Thiolate Perturbation in Cystathionine β-Synthase by Mercury Compounds.","description":"Cystathionine β-synthase (CBS) is an enzyme involved in sulfur metabolism that catalyzes the pyridoxal phosphate-dependent condensation of homocysteine with serine or cysteine to form cystathionine and water or hydrogen sulfide (H<sub>2</sub>S), respectively. CBS possesses a <i>b</i>-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 (HgCl<sub>2</sub>) and <i>p</i>-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 0.3-0.4 s<sup>-1</sup> for Fe(III)-CBS and 40 ± 4 s<sup>-1</sup> 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 HgCl<sub>2</sub> led to heme release and activity loss. Our study reveals the complexity of the interactions between mercury compounds and CBS.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Jan","modification":"2024-11-13T04:01:06.38Z","creation":"2021-02-21T05:24:21Z"},"accession":"S-EPMC7841933","cross_references":{"pubmed":["33521459"],"doi":["10.1021/acsomega.0c05475"]}}