title: Kinetic investigations with inhibitors that mimic the posthomolysis intermediate in the reactions of coenzyme-B12-dependent glycerol dehydratase and diol dehydratase.
abstract: Kinetic investigations were performed on the coenzyme-B12-dependent glycerol dehydratase and diol dehydratase reactions using 1,2-propanediol as substrate and [omega-(adenosin-5'-O-yl)alkyl]cobalamins as mimics of the posthomolysis intermediate state of the coenzyme. All the coenzyme-B12 analogues with oligomethylene chains (C3-C7) inserted between the central Co atom and the 5' O of the adenosine moiety were competitive inhibitors with respect to coenzyme B12. The apparent inhibition constants (Ki) of the shorter-chain inhibitors, especially the C5 inhibitor, were smaller for both enzymes than those of the longer-chain (C6, C7) compounds. These results are in agreement with the expected (0.6-0.9 nm) distance between the Co and 5'-methylene paramagnetic centers in the posthomolysis intermediate state of coenzyme B12 in these reactions.
authors.affiliation: Department of Biochemistry, Institute of Organic Chemistry, University of Karlsruhe, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Poppe
authors.forename: J
authors.initials: J
authors.lastname: Rétey
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism; D001667:Binding, Competitive; D002384:Catalysis; D002954:Citrobacter; D003038:Cobamides / Q000737:chemistry / Q000378:metabolism*; D045728:Corrinoids; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000378:metabolism*; D004926:Escherichia coli; D006836:Hydro-Lyases / Q000378:metabolism*; D007536:Isomerism; D007700:Kinetics; D014677:Pharmaceutical Vehicles / Q000378:metabolism; D011166:Porphyrins / Q000378:metabolism; D011408:Propanediol Dehydratase / Q000378:metabolism*; D019946:Propylene Glycol; D011409:Propylene Glycols / Q000378:metabolism; D011487:Protein Conformation; D012486:Salmonella typhimurium
chemical_list: D000975:Antioxidants; D003038:Cobamides; D045728:Corrinoids; D004791:Enzyme Inhibitors; D014677:Pharmaceutical Vehicles; D011166:Porphyrins; D011409:Propylene Glycols; D019946:Propylene Glycol; D006836:Hydro-Lyases; D011408:Propanediol Dehydratase; C020671:glycerol dehydratase; C000913:cobamamide; D000241:Adenosine