Roles of the Active Site Zn(II) and Residues in Substrate Discrimination by Threonyl-tRNA Synthetase: An MD and QM/MM Investigation

2017 ◽  
Vol 121 (25) ◽  
pp. 6163-6174 ◽  
Author(s):  
Mohamed M. Aboelnga ◽  
James W. Gauld
Keyword(s):  
Active Site ◽  
Trna Synthetase ◽  
Substrate Discrimination

scholarly journals Transcription and translation in an RNA world

2006 ◽  
Vol 361 (1474) ◽  
pp. 1751-1760 ◽  
Author(s):  
William R Taylor
Keyword(s):  
Amino Acid ◽  
Active Site ◽  
Rna World ◽  
Large Subunit ◽  
Trna Synthetase ◽  
Nucleoside Triphosphate ◽  
Amino Acid Binding ◽  
World Hypothesis ◽  
Protein Elongation ◽  
Rna World Hypothesis

The RNA world hypothesis requires a ribozyme that was an RNA-directed RNA polymerase (ribopolymerase). If such a replicase makes a reverse complementary copy of any sequence (including itself), in a simple RNA world, there is no mechanism to prevent self-hybridization. It is proposed that this can be avoided through the synthesis of a parallel complementary copy. The logical consequences of this are pursued and developed in a computer simulation, where the behaviour of the parallel copy is compared to the conventional reverse complementary copy. It is found that the parallel copy is more efficient at higher temperatures (up to 90°C). A model for the ribopolymerase, based on the core of the large subunit (LSU) of the ribosome, is described. The geometry of a potential active site for this ribopolymerase suggests that it contained a cavity (now occupied by the aminoacyl-tRNA) and that an amino acid binding in this might have ‘poisoned’ the ribopolymerase by cross-reacting with the nucleoside-triphosphate before polymerization could occur. Based on a similarity to the active site components of the class-I tRNA synthetase enzymes, it is proposed that the amino acid could become attached to the nascent RNA transcript producing a variety of aminoacylated tRNA-like products. Using base-pairing interactions, some of these molecules might cross-link two ribopolymerases, giving rise to a precursor of the modern ribosome. A hybrid dimer, half polymerase and half proto-ribosome, could account for mRNA translocation before the advent of protein elongation factors.

Active Site of Lysyl-tRNA Synthetase:  Structural Studies of the Adenylation Reaction†

Biochemistry ◽  
2000 ◽  
Vol 39 (29) ◽  
pp. 8418-8425 ◽  
Author(s):  
Gianluigi Desogus ◽  
Flavia Todone ◽  
Peter Brick ◽  
Silvia Onesti
Keyword(s):  
Active Site ◽  
Trna Synthetase ◽  
Structural Studies

scholarly journals The relationship between synthetic and editing functions of the active site of an aminoacyl-tRNA synthetase.

1993 ◽  
Vol 90 (24) ◽  
pp. 11553-11557 ◽  
Author(s):  
H. Y. Kim ◽  
G. Ghosh ◽  
L. H. Schulman ◽  
S. Brunie ◽  
H. Jakubowski
Keyword(s):  
Active Site ◽  
Trna Synthetase ◽  
Aminoacyl Trna Synthetase ◽  
The Relationship

scholarly journals Active-Site Assembly in Glutaminyl-tRNA Synthetase by tRNA-Mediated Induced Fit†

Biochemistry ◽  
2006 ◽  
Vol 45 (22) ◽  
pp. 6858-6865 ◽  
Author(s):  
Nathan T. Uter ◽  
John J. Perona
Keyword(s):  
Active Site ◽  
Trna Synthetase ◽  
Induced Fit

scholarly journals Crystal structures of the editing domain of Escherichia coli leucyl-tRNA synthetase and its complexes with Met and Ile reveal a lock-and-key mechanism for amino acid discrimination

2006 ◽  
Vol 394 (2) ◽  
pp. 399-407 ◽  
Author(s):  
Yunqing Liu ◽  
Jing Liao ◽  
Bin Zhu ◽  
En-Duo Wang ◽  
Jianping Ding
Keyword(s):  
Escherichia Coli ◽  
Amino Acids ◽  
Crystal Structures ◽  
Active Site ◽  
Binding Pocket ◽  
Trna Synthetase ◽  
Vital Role ◽  
Common Mechanism ◽  
Trna Synthetases ◽  
Editing Domain

aaRSs (aminoacyl-tRNA synthetases) are responsible for the covalent linking of amino acids to their cognate tRNAs via the aminoacylation reaction and play a vital role in maintaining the fidelity of protein synthesis. LeuRS (leucyl-tRNA synthetase) can link not only the cognate leucine but also the nearly cognate residues Ile and Met to tRNALeu. The editing domain of LeuRS deacylates the mischarged Ile–tRNALeu and Met–tRNALeu. We report here the crystal structures of ecLeuRS-ED (the editing domain of Escherichia coli LeuRS) in both the apo form and in complexes with Met and Ile at 2.0 Å, 2.4 Å, and 3.2 Å resolution respectively. The editing active site consists of a number of conserved amino acids, which are involved in the precise recognition and binding of the noncognate amino acids. The substrate-binding pocket has a rigid structure which has an optimal stereochemical fit for Ile and Met, but has steric hindrance for leucine. Based on our structural results and previously available biochemical data, we propose that ecLeuRS-ED uses a lock-and-key mechanism to recognize and discriminate between the amino acids. Structural comparison also reveals that all subclass Ia aaRSs share a conserved structure core consisting of the editing domain and conserved residues at the editing active site, suggesting that these enzymes may use a common mechanism for the editing function.

scholarly journals The aminoacylation of transfer ribonucleic acid. Recognition of methionine by Escherichia coli methionyl-transfer ribonucleic acid synthetase

1977 ◽  
Vol 165 (2) ◽  
pp. 367-373 ◽  
Author(s):  
J M Old ◽  
D S Jones
Keyword(s):  
Escherichia Coli ◽  
Active Site ◽  
Ribonucleic Acid ◽  
Chemical Nature ◽  
Trna Synthetase ◽  
Side Chain ◽  
Amino Acid Side Chain ◽  
Sulphur Atom ◽  
Recognition Mechanism ◽  
Methionyl Trna Synthetase

The mechanism of the recognition of methionine by Escherichia coli methionyl-tRNA synthetase was examined by a kinetic study of the recognition of methionine analogues in the ATP-PPi exchange reaction and the tRNA-aminoacylation reaction. The results show that the recognition mechanism consists of three parts: (1) the recognition of the size, shape and chemical nature of the amino acid side chain at the methionine-binding stage of the reaction; (2) the recognition of the length of the side chain at the stage of aminoacyl-adenylate complex-formation; (3) the recognition of the sulphur atom in the side chain at the stage of methionyl-tRNA formation. It is proposed that the sulphur atom interacts with the enzyme to induce a conformational change. A model of the active site incorporating the mechanism of methionine recognition is presented.

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