Inhibition of cobalamin‐dependent methionine synthase by substituted benzo‐fused heterocycles

• Published in: The FEBS journal Vol. 274; no. 1; pp. 287 - 299
• Main Authors: Banks, Elizabeth C., Doughty, Stephen W., Toms, Steven M., Wheelhouse, Richard T., Nicolaou, Anna
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2007
• Subjects: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - antagonists & inhibitors; 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - chemistry; Amino Acid Sequence; Animals; benzimidazole; Benzimidazoles - chemical synthesis; Benzimidazoles - pharmacology; benzothiadiazole; Binding Sites; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Enzymes; Hydrogen Bonding; Hydrogen bonds; inhibition; Inhibitor drugs; Kinetics; Liver; Liver - enzymology; methionine synthase; Models, Molecular; molecular modelling; Molecular Sequence Data; Molecular structure; Pharmacology; Rats; Rodents; Sequence Homology; Signal transduction; Structure-Activity Relationship; Tetrahydrofolates - chemistry; Tetrahydrofolates - metabolism; Thiadiazoles - chemistry; Thiadiazoles - pharmacology

The cobalamin–dependent cytosolic enzyme, methionine synthase (EC.2.1.1.13), catalyzes the remethylation of homocysteine to methionine using 5‐methyltetrahydrofolate as the methyl donor. The products of this remethylation – methionine and tetrahydrofolate – participate in the active methionine and f...