Ochratoxin binding to phenylalanyl-tRNA synthetase: Computational approach to the mechanism of ochratoxicosis and its antagonism

Journal of Medicinal Chemistry

Volumn 42, Issue 16, 1999, Pages 3075-3086

  McMasters, Daniel R ^a   Vedani, Angelo ^a  

^a Biographics Laboratory 3R   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ASPARTAME; OCHRATOXIN; PHENYLALANINE TRANSFER RNA LIGASE; PIROXICAM;

ARTICLE; BINDING AFFINITY; BINDING KINETICS; CRYSTAL STRUCTURE; ENZYME BINDING; NONHUMAN; THERMUS THERMOPHILUS; TOXIN ANALYSIS; TOXIN STRUCTURE;

BINDING SITES; HUMANS; MODELS, MOLECULAR; OCHRATOXINS; PHENYLALANINE-TRNA LIGASE; PROTEIN BINDING; PROTEIN CONFORMATION; SERUM ALBUMIN;

EID: 0033549897     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm991040k     Document Type: Article

References (53)

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48. While the amino acid substrate (FAMP) is identical for PheRS in all species, the cognate tRNA is not. Further, the importance of proofreading in translation fidelity has been reported to increase during evolution (Gabius, H.-J.; von der Haar, F.; Cramer, F. Evolutionary Aspects of Accuracy of Phenylalanyl-tRNA Synthetase. A Comparative Study with Enzymes from Escherichia coli, Saccharomyces cerevisiae, Neurospora crassa, and Turkey Liver using Phenylalanine Analogues. Biochemistry 1983, 22, 2231-2339). Differences in sequence are therefore likely to serve tRNA recognition and proofreading mechanisms.
49. It is interesting to note in this regard that of all those residues directly involved in binding, only one is conserved between B. subtilis and S. cerevisiae (which showed inhibition by OA) yet different for E. coli (which showed no inhibition), namely at the position corresponding to Trp149 in T. thermophilus, which is a His in E. coli but a GIn in B. subtilis and S. cerevisiae. This residue is also occupied by His in the putative human PheRS.
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