Methionine synthase catalysis

Evans JC, Huddler DP, Hilgers MT, Romanchuk G, Matthews RG, Ludwig ML. (2004) Structures of the N-terminal modules imply large domain motions during catalysis by methionine synthase. Proc Natl Acad Sd USA 101 3729-3736. 

Figure 2, Catalysis and reactivation of methionine synthase. Methionine for,motion occurs via two half reactions in which cobalamin serves as the intermediate methyl carrier. Reactivation is depicted in the right-hand portion of the diagram. An electron donor and AdoMet convert the inactive cob(II)alamin form of the enzyme to methylcob(III)alamin. In E. colU flavodoxin serves as the reductant for this priming reaction (7).

Cystathionine y-synthase (CGS) is a rather unique PLP-enzyme that catalyzes a transsulfuration reaction important in microbial methionine biosynthesis. It is the only known enzyme whose function is the catalysis of a PLP-dependent replacement reaction at the y-carbon of the amino acid substrate the succinyl moiety of O-succinyl-L-homoserine is replaced by i-Cys to give the thioether linkage of L,/.-cystathionine (scheme II). In the absence of L-Cys, the enzyme catalyzes a net y-elimination reaction from OSHS (scheme II). Because both reactions require the elimination of succinate, the catalytic pathways must diverge from a common reaction intermediate. It was originally hypothesized that a vinylglycine quinonoidal intermediate (structure 11)... 

Among these polyamines, putrescine is biosynthesized from ornithine by decarboxylation with ornithine decarboxylase. Putrescine receives a propyl-amino rmit (C3N unit) from decarboxylated SAM (S-adenosylmethionine) to form spermidine. SAM is derived from methionine. Spermidine synthase catalyzes this biosynthetic process. Spermine is formed from spermidine through the addition of a C3N unit from a decarboxylated SAM unit under the catalysis of spermine synthase [3]. 

Putrescine, which is produced by decarboxylation of ornithine, and also arises from agmatine with catalysis by agmatinase, becomes the starting compound for the biosynthesis of spermidine and spermine. These reactions are catalysed by spermidine synthase and spermine synthase, respectively, involving S-adenosyl-L-methionine (for short AdoMet or SAM), and take place from bacteria to mammals (Figure 10.16). S-Adenosyl-L-methionine amide (dSAM) formed by decarboxylation of SAM provides trimethylene amine residue for this biosynthesis, which yields S-methyl-5 -thioadenosine (MTA). 

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