scholarly journals Editing Domain Motions Preorganize the Synthetic Active Site of Prolyl-tRNA Synthetase

ACS Catalysis ◽  
2020 ◽  
Vol 10 (17) ◽  
pp. 10229-10242
Author(s):  
Quin H. Hu ◽  
Murphi T. Williams ◽  
Irina Shulgina ◽  
Carl J. Fossum ◽  
Katelyn M. Weeks ◽  
...  
Keyword(s):  
Active Site ◽  
Trna Synthetase ◽  
Editing Domain ◽  
Domain Motions

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 Study on the putative active site of Enterococcus faecalis prolyl- tRNA synthetase editing domain by methods of site-directed mutagenesis

2009 ◽  
Vol 25 (1) ◽  
pp. 39-42 ◽  
Author(s):  
K. S. Boyarshin ◽  
I. A. Kriklivyi ◽  
A. V. Rayevsky ◽  
A. A. Himin ◽  
A. D. Yaremchuk ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Active Site ◽  
Trna Synthetase ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Putative Active Site ◽  
Editing Domain

Interdomain communication modulates the tRNA-dependent pre-transfer editing of leucyl-tRNA synthetase

2012 ◽  
Vol 449 (1) ◽  
pp. 123-131 ◽  
Author(s):  
Min Tan ◽  
Bin Zhu ◽  
Ru-Juan Liu ◽  
Xin Chen ◽  
Xiao-Long Zhou ◽  
...  
Keyword(s):  
Active Site ◽  
Control Mechanism ◽  
Trna Synthetase ◽  
Structural Studies ◽  
Conformational Rearrangement ◽  
X Ray ◽  
Editing Domain ◽  
Crystal Structural ◽  
Quality Control Mechanism ◽  
Interdomain Communication

EcLeuRS [Escherichia coli LeuRS (leucyl-tRNA synthetase)] has evolved both tRNA-dependent pre- and post-transfer editing capabilities to ensure catalytic specificity. Both editing functions rely on the entry of the tRNA CCA tail into the editing domain of the LeuRS enzyme, which, according to X-ray crystal structural studies, leads to a dynamic disordered orientation of the interface between the synthetic and editing domains. The results of the present study show that this tRNA-triggered conformational rearrangement leads to interdomain communication between the editing and synthetic domains through their interface, and this communication mechanism modulates the activity of tRNA-dependent pre-transfer editing. Furthermore, tRNA-dependent editing reaction inhibits misactivating non-cognate amino acids from the synthetic active site. These results also suggested a novel quality control mechanism of EcLeuRS which is achieved through the co-ordination between the synthetic and editing domains.

A naturally occurring nonapeptide functionally compensates for the CP1 domain of leucyl-tRNA synthetase to modulate aminoacylation activity

2012 ◽  
Vol 443 (2) ◽  
pp. 477-484 ◽  
Author(s):  
Min Tan ◽  
Wei Yan ◽  
Ru-Juan Liu ◽  
Meng Wang ◽  
Xin Chen ◽  
...  
Keyword(s):  
Catalytic Efficiency ◽  
Trna Synthetase ◽  
Modular Construction ◽  
Aquifex Aeolicus ◽  
Trna Synthetases ◽  
Naturally Occurring ◽  
Aminoacyl Trna Synthetases ◽  
Editing Domain ◽  
Editing Activity ◽  
Shed Light

aaRSs (aminoacyl-tRNA synthetases) establish the rules of the genetic code by catalysing the formation of aminoacyl-tRNA. The quality control for aminoacylation is achieved by editing activity, which is usually carried out by a discrete editing domain. For LeuRS (leucyl-tRNA synthetase), the CP1 (connective peptide 1) domain is the editing domain responsible for hydrolysing mischarged tRNA. The CP1 domain is universally present in LeuRSs, except MmLeuRS (Mycoplasma mobile LeuRS). The substitute of CP1 in MmLeuRS is a nonapeptide (MmLinker). In the present study, we show that the MmLinker, which is critical for the aminoacylation activity of MmLeuRS, could confer remarkable tRNA-charging activity on the inactive CP1-deleted LeuRS from Escherichia coli (EcLeuRS) and Aquifex aeolicus (AaLeuRS). Furthermore, CP1 from EcLeuRS could functionally compensate for the MmLinker and endow MmLeuRS with post-transfer editing capability. These investigations provide a mechanistic framework for the modular construction of aaRSs and their co-ordination to achieve catalytic efficiency and fidelity. These results also show that the pre-transfer editing function of LeuRS originates from its conserved synthetic domain and shed light on future study of the mechanism.

scholarly journals Evolutionary Basis for the Coupled-domain Motions inThermus thermophilusLeucyl-tRNA Synthetase

2009 ◽  
Vol 284 (15) ◽  
pp. 10088-10099 ◽  
Author(s):  
Kristina Mary Ellen Weimer ◽  
Brianne Leigh Shane ◽  
Michael Brunetto ◽  
Sudeep Bhattacharyya ◽  
Sanchita Hati
Keyword(s):  
Trna Synthetase ◽  
Domain Motions

scholarly journals The design of active site inhibitors ofMycobacterium tuberculosistyrosyl-tRNA synthetase based on SB-219383 inhibitor

2014 ◽  
pp. 167-174 ◽  
Author(s):  
V.V. Mykuliak ◽  
◽  
I.Ya. Dubey ◽  
A.I. Kornelyuk ◽  
◽  
...  
Keyword(s):  
Active Site ◽  
Trna Synthetase

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.

Deciphering the interaction of benzoxaborole inhibitor AN2690 with connective polypeptide 1 (CP1) editing domain of Leishmania donovani leucyl-tRNA synthetase

2020 ◽  
Vol 45 (1) ◽  
Author(s):  
Smriti Tandon ◽  
Reetika Manhas ◽  
Neha Tiwari ◽  
Manoj Munde ◽  
Ramachandran Vijayan ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Trna Synthetase ◽  
Editing Domain

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
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