Escherichia coli tRNA (uracil-5-)-methyltransferase: Inhibition by analogues of adenosylhomocysteine. 1979

L Shugart, and B Chastain

Structural analogues of adenosylhomocysteine (AdoHcy) have been tested as inhibitors of a tRNA(uracil-5-)-methyltransferase preparation obtained from Escherichia coli. All analogues tested gave linear competitive inhibition kinetics with adenosylmethionine (AdoMet) as the variable substrate. Comparison of the Ki values obtained leads to the following conclusions concerning the specificity of the AdoMet-AdoHcy binding site on the enzyme: (i) the terminal amino group of the amino acid moiety is necessary for activity; (ii) both a chiral change of the asymmetric carbon atom of homocysteine and the presence of the terminal carboxyl group contribute little towards inhibitory activity; (iii) analogues in which the amino function of the adenyl moiety is modified or substituted are still potent inhibitors; (iv) inhibitor specificity is considerably reduced when adenine is replaced by a pyrimidine base.

UI MeSH Term Description Entries
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D006710 Homocysteine A thiol-containing amino acid formed by a demethylation of METHIONINE. 2-amino-4-mercaptobutyric acid,Homocysteine, L-Isomer,2 amino 4 mercaptobutyric acid,Homocysteine, L Isomer,L-Isomer Homocysteine
D000596 Amino Acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Amino Acid,Acid, Amino,Acids, Amino
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D012359 tRNA Methyltransferases Enzymes that catalyze the S-adenosyl-L-methionine-dependent methylation of ribonucleotide bases within a transfer RNA molecule. EC 2.1.1. RNA Methylase,RNA Methylases,RNA, Transfer, Methyltransferases,T RNA Methyltransferases,tRNA Methyltransferase,Methylase, RNA,Methylases, RNA,Methyltransferase, tRNA,Methyltransferases, T RNA,Methyltransferases, tRNA,RNA Methyltransferases, T
D012435 S-Adenosylhomocysteine 5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions. S Adenosylhomocysteine,Adenosylhomocysteine, S
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

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