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Here we demonstrate with a range of experimental approaches using cell lines, in vitro systems, and recombinantly expressed enzyme, that human methyltransferase-like protein 7B (METTL7B) catalyzes the transfer of a methyl group from\n                    <jats:italic>S-<\/jats:italic>\n                    adenosyl-\n                    <jats:sc>l<\/jats:sc>\n                    -methionine (AdoMet) to hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) and other exogenous thiol small molecules.\n                    <jats:italic>METTL7B<\/jats:italic>\n                    gene modulation experiments, including knockdown in HepG2 cells and overexpression in HeLa cells, directly alter the methylation of the drug captopril, a historic probe substrate for TMT activity. Furthermore, recombinantly expressed and purified wild-type METTL7B methylates several thiol compounds, including H\n                    <jats:sub>2<\/jats:sub>\n                    S, 7\u03b1-thiospironolactone,\n                    <jats:sc>l<\/jats:sc>\n                    -penicillamine, and captopril, in a time- and concentration-dependent manner. Typical for AdoMet-dependent small molecule methyltransferases,\n                    <jats:italic>S<\/jats:italic>\n                    -adenosyl-\n                    <jats:sc>l<\/jats:sc>\n                    -homocysteine (AdoHcy) inhibited METTL7B activity in a competitive fashion. Similarly, mutating a conserved aspartate residue, proposed to anchor AdoMet into the active site, to an alanine (D98A) abolished methylation activity. Endogenous thiols such as glutathione and cysteine, or classic substrates for other known small molecule\n                    <jats:italic>S<\/jats:italic>\n                    -,\n                    <jats:italic>N<\/jats:italic>\n                    -, and\n                    <jats:italic>O<\/jats:italic>\n                    -methyltransferases, were not substrates for METTL7B. Our results confirm, for the first time, that\n                    <jats:italic>METTL7B<\/jats:italic>\n                    , a gene implicated in multiple disease states including rheumatoid arthritis and breast cancer, encodes a protein that methylates small molecule alkyl thiols. Identifying the catalytic function of METTL7B will enable future pharmacological research in disease pathophysiology where altered\n                    <jats:italic>METTL7B<\/jats:italic>\n                    expression and, potentially H\n                    <jats:sub>2<\/jats:sub>\n                    S levels, can disrupt cell growth and redox state.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-84218-5","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T06:07:32Z","timestamp":1614578852000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Human METTL7B is an alkyl thiol methyltransferase that metabolizes hydrogen sulfide and captopril"],"prefix":"10.1038","volume":"11","author":[{"given":"Benjamin J.","family":"Maldonato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drake A.","family":"Russell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rheem A.","family":"Totah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,1]]},"reference":[{"key":"84218_CR1","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1007\/s002280000137","volume":"56","author":"T Kr\u00f6plin","year":"2000","unstructured":"Kr\u00f6plin, T. & Iven, H. 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