Abstract
Summary Paragraph/AbstractMethyltransferase-like protein 7B (METTL7B) is implicated in tumor growth and progression while gene expression is upregulated in several different disease states such as rheumatoid arthritis and breast cancer. Yet, the catalytic function of METTL7B has not been characterized. Here we demonstrate thatMETTL7Bencodes a protein that catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to hydrogen sulfide (H2S) to form methanethiol (CH3SH). Several exogenous aliphatic thiols were also identified as substrates. Modulation ofMETTL7Bgene expression in HepG2 and HeLa cell culture directly alters the methylation of captopril, a marker reaction of alkyl thiol methyltransferase (TMT) activity(1, 2). Furthermore, cloned and recombinantly expressed and purified METTL7B full length protein methylates several thiol compounds, including hydrogen sulfide, 7α-thiospironolactone, captopril, and L-penicillamine in a concentration dependent manner. Endogenous thiols such as glutathione and cysteine or classic probe substrates of other known small moleculeS-,N-, andO- methyltransferases were not substrates for METTL7B. Our results unequivocally demonstrate, and for the first time, that METTL7B, a protein implicated in several disease states, is an alkyl thiol methyltransferase(3–5). Identifying the catalytic function of METTL7B will enable future pharmacological research in disease pathophysiology whereMETTL7Bexpression and H2S levels can potentially alter the redox state and growth cycle of cells.
Publisher
Cold Spring Harbor Laboratory
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