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Molecular recognition of tyrosinyl adenylate analogues by prokaryotic tyrosyl tRNA synthetases.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 1999 Nov; Vol. 7 (11), pp. 2473-85. - Publication Year :
- 1999
-
Abstract
- Molecular modelling and synthetic studies have been carried out on tyrosinyl adenylate and analogues to probe the interactions seen in the active site of the X-ray crystal structure of tyrosyl tRNA synthetase from Bacillus stearothermophilus, and to search for new inhibitors of this enzyme. Micromolar and sub-micromolar inhibitors of tyrosyl tRNA synthetases from both B. stearothermophilus and Staphylococcus aureus have been synthesised. The importance of the adenine ring to the binding of tyrosinyl adenylate to the enzyme, and the importance of water-mediated hydrogen bonding interactions, have been highlighted. The inhibition data has been further supported by homology modelling with the S. aureus enzyme, and by ligand docking studies.
- Subjects :
- Adenine metabolism
Adenosine Monophosphate chemistry
Adenosine Monophosphate metabolism
Amino Acid Sequence
Binding Sites
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors chemistry
Enzyme Inhibitors pharmacology
Geobacillus stearothermophilus genetics
Models, Molecular
Molecular Sequence Data
Phosphates metabolism
Protein Binding
Ribose metabolism
Sequence Homology, Amino Acid
Staphylococcus aureus enzymology
Staphylococcus aureus genetics
Tyrosine chemistry
Tyrosine metabolism
Tyrosine-tRNA Ligase antagonists & inhibitors
Tyrosine-tRNA Ligase genetics
Adenosine Monophosphate analogs & derivatives
Geobacillus stearothermophilus enzymology
Tyrosine analogs & derivatives
Tyrosine-tRNA Ligase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0968-0896
- Volume :
- 7
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 10632057
- Full Text :
- https://doi.org/10.1016/s0968-0896(99)00192-3