Methionine gamma-lyase (MGL) is an enzyme in the γ-family of PLP-dependent enzymes. It degrades sulfur-containing amino acids to α-keto acids, ammonia, and thiols. Because sulfur-containing amino acids play a role in multiple biological processes, the regulation of these amino acids is essential. Additionally, it is crucial to maintain low homocysteine levels for the proper functioning of various pathways and for preventing the toxic effects of the cysteine homologue. Methionine gamma-lyase has been found in several bacteria (Clostridiums porogenes, Pseudomonas ovalis, Pseudomonas putida, Aeromonas sp., Citrobacter intermedius, Brevibacterium linens, Citrobacter freundii, Porphyromonas gingivalis, Treponema denticola), parasitic protozoa (Trichomonas vaginalis, Entamoeba histolytica), and plants (Arabidopsis thaliana).

This enzyme belongs to the family of lyases, specifically the class of carbon-sulfur lyases. The systematic name of this enzyme class is L-methionine methanethiol-lyase (deaminating 2-oxobutanoate-forming). Other names in common use include L-methioninase, methionine lyase, methioninase, methionine dethiomethylase, L-methionine gamma-lyase, and L-methionine methanethiol-lyase (deaminating). This enzyme participates in selenoamino acid metabolism. It employs one cofactor, pyridoxal phosphate.

The enzyme is made up of 389-441 amino acids and forms four identical subunits. The active molecule is composed of two tightly associated dimers, the interface at which lies the active site. Each of the dimers has a pyridoxal 5’-phosphate (PLP) cofactor. Six amino acids located near the active site are involved in the reaction, namely Tyr59, Arg61, Tyr114, Cys116, Lys240, and Asp241. Unlike the other amino acids, Cys116 is not typically found in PLP γ-family enzymes, which instead have glycine or proline. Although there is no direct contact between Cys116 and either MGL or the methionine substrate, studies show that the amino acid is involved in retaining substrate specificity.

In enzymology, a methionine gamma-lyase (EC 4.4.1.11) is an enzyme that catalyzes the chemical reaction

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