Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.1.1.20 (phenylalanyl-tRNA synthetase)
 358 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because of its chiralic alpha-phosphorus atom adenosine 5'-O-(1-thiotriphosphate) (ATPalphaS) exists in two diastereomeric forms, arbitrarily named (A) and (B). For phenylalanyl-tRNA synthetase ATPalphaS (A) is a substrate whereas ATPalphaS (B) is neither a substrate nor an inhibitor. During the ATPalphaS (A)/PPi exchange reaction with phenylalanyl-tRNA synthetase the configuration at the alpha-phosphorus is retained. The mechanistic implications of these findings are discussed. Preliminary investigations with several other aminoacyl-tRNA synthetases show that the stereochemical requirement with respect to the alpha-phosphorus of ATP is not identical for all aminoacyl-tRNA synthetases.
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PMID:On the stereochemistry of activation of phenylalanine by phenylalanyl-tRNA synthetase from baker's yeast. 32 81

The activation of L-phenylalanine by yeast phenylalanyl-tRNA synthetase using adenosine 5'-[(S)-alpha-17O,alpha,alpha-18O2]triphosphate is shown to proceed with inversion of configuration at P alpha of ATP. This observation taken together with the lack of positional isotope exchange when adenosine 5'-[beta,beta-18O2]triphosphate is incubated with the enzyme in the absence of phenylalanine and in the presence of the competitive inhibitor phenylalaninol indicates that activation of phenylalanine occurs by a direct "in-line" adenylyl-transfer reaction. In the presence of Zn2+, yeast phenylalanyl-tRNA synthetase also catalyzes the phenylalanine-dependent hydrolysis of ATP to AMP and the synthesis of P1,P4-bis(5'-adenosyl) tetraphosphate (Ap4A). With adenosine 5'-[(S)-alpha-17O,alpha,alpha-18O2]triphosphate, the formation of AMP and Ap4A is shown to occur with inversion and retention of configuration, respectively. It is concluded that phenylalanyl adenylate is an intermediate in both processes, Zn2+ promoting AMP formation by hydrolytic cleavage of the C-O bond and Ap4A formation by displacement at phosphorus of phenylalanine by ATP.
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PMID:Mechanism of activation of phenylalanine and synthesis of P1, P4-bis(5'-adenosyl) tetraphosphate by yeast phenylalanyl-tRNA synthetase. 389 31

Negative ion fast atom bombardment mass spectrometry has been used to distinguish between (Sp)-adenosine 5'-O-(1-thiotriphosphate) containing either an alpha- nonbridging or an alpha-beta-bridging 18O label. The method does not require any nucleotide derivatization and so avoids the excessive manipulations and purifications necessary to distinguish between the above two species using conventional mass spectroscopy. Furthermore, it is between 50 and 200 times more sensitive than other direct methods based on 31P nuclear magnetic resonance spectroscopy. Routinely, 100 nmol of nucleoside phosphorothioate is ample to establish the 18O isotope position by normal as well as linked scan mass spectrometry. In cases where normal mass spectrometry is considered adequate, 10 nmol of material suffices. This technique should be useful in determining the stereochemical course of enzymatic nucleotidyl transfer and nuclease-catalyzed hydrolysis reactions under conditions of limiting availability of enzyme or substrate. Yeast phenylalanyl-tRNA synthetase was used to prepare the 18O-labeled adenosine 5'-O-(1-thiotriphosphate) species, and this enzyme was concomitantly shown to catalyze adenylyl transfer with inversion of configuration at phosphorus.
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PMID:Direct mass spectroscopic method for determination of oxygen isotope position in adenosine 5'-O-(1-thiotriphosphate). Determination of the stereochemical course of the yeast phenylalanyl-tRNA synthetase reaction. 637 64