Molecular recognition of tyrosinyl adenylate analogues by prokaryotic tyrosyl tRNA synthetases.

Brown P; Richardson CM; Mensah LMOHanlon PJOsborne NFPope AJWalker G

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Molecular recognition of tyrosinyl adenylate analogues by prokaryotic tyrosyl tRNA synthetases.

机译：Molecular recognition of tyrosinyl adenylate analogues by prokaryotic tyrosyl tRNA synthetases.

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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.

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《Bioorganic and medicinal chemistry》 |1999年第11期|2473-2485|共13页
作者
Brown P; Richardson CM; Mensah LMOHanlon PJOsborne NFPope AJWalker G;
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SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK.;

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正文语种英语
中图分类药学;生物化学;
关键词
Adenosine Monophosphate; Bacillus stearothermophilus; Tyrosine; Tyrosine tRNA Ligase metabolism; 腺苷一磷酸; 芽孢杆菌; 嗜热脂肪; 酪氨酸;

Molecular recognition of tyrosinyl adenylate analogues by prokaryotic tyrosyl tRNA synthetases.

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