scholarly journals Amino Acid Residues Required for Maturation, Cell Uptake, and Processing of Translation Inhibitor Microcin C

2006 ◽  
Vol 189 (5) ◽  
pp. 2114-2118 ◽  
Author(s):  
Teymur Kazakov ◽  
Anastasia Metlitskaya ◽  
Konstantin Severinov
Keyword(s):  
Amino Acid ◽  
Trna Synthetase ◽  
Trojan Horse ◽  
Cell Uptake ◽  
Amino Acid Residues ◽  
Peptide Moiety ◽  
Translation Inhibitor ◽  
Mutational Study ◽  
The Way

ABSTRACT Microcin C (McC), a peptide-nucleotide Trojan horse antibiotic, targets aspartyl-tRNA synthetase. We present the results of a systematic mutational study of the 7-amino-acid ribosomally synthesized peptide moiety of McC. Our results define amino acid positions important for McC maturation and cell uptake and processing and open the way for creation of more potent McC-based inhibitors.

scholarly journals Identification of potential amino acid residues supporting anticodon recognition in yeast methionyl-tRNA synthetase

FEBS Letters ◽  
1991 ◽  
Vol 289 (2) ◽  
pp. 217-220 ◽  
Author(s):  
Laurence Despons ◽  
Philippe Walter ◽  
Bruno Senger ◽  
Jean-Pierre Ebel ◽  
Franco Fasiolo
Keyword(s):  
Amino Acid ◽  
Trna Synthetase ◽  
Amino Acid Residues ◽  
Methionyl Trna Synthetase

Limited Set of Amino Acid Residues in a Class Ia Aminoacyl-tRNA Synthetase Is Crucial for tRNA Binding†

Biochemistry ◽  
2003 ◽  
Vol 42 (51) ◽  
pp. 15092-15101 ◽  
Author(s):  
Renaud Geslain ◽  
Gilbert Bey ◽  
Jean Cavarelli ◽  
Gilbert Eriani
Keyword(s):  
Amino Acid ◽  
Trna Synthetase ◽  
Amino Acid Residues ◽  
Aminoacyl Trna Synthetase ◽  
Trna Binding

Human cytoplasmic ProX edits mischarged tRNAPro with amino acid but not tRNA specificity

2013 ◽  
Vol 450 (1) ◽  
pp. 243-252 ◽  
Author(s):  
Liang-Liang Ruan ◽  
Xiao-Long Zhou ◽  
Min Tan ◽  
En-Duo Wang
Keyword(s):  
Amino Acid ◽  
Protein Biosynthesis ◽  
Trna Synthetase ◽  
Main Body ◽  
Amino Acid Residues ◽  
Homologous Proteins ◽  
Gene Encoding ◽  
Trna Synthetases ◽  
Editing Domain ◽  
First Time

aaRSs (aminoacyl-tRNA synthetases) are responsible for ensuring the fidelity of the genetic code translation by accurately linking a particular amino acid to its cognate tRNA isoacceptor. To ensure accuracy of protein biosynthesis, some aaRSs have evolved an editing process to remove mischarged tRNA. The hydrolysis of the mischarged tRNA usually occurs in an editing domain, which is inserted into or appended to the main body of the aaRS. In addition, autonomous, editing domain-homologous proteins can also trans-edit mischarged tRNA in concert or in compensating for the editing function of its corresponding aaRS. The freestanding ProX is a homologue of the editing domain of bacterial ProRS (prolyl-tRNA synthetase). In the present study, we cloned for the first time a gene encoding HsProX (human cytoplasmic ProX) and purified the expressed recombinant protein. The catalytic specificity of HsProX for non-cognate amino acids and identity elements on tRNAPro for editing were also investigated. We found that HsProX could deacylate mischarged Ala-tRNAPro, but not Cys-HstRNAUGGPro, and specifically targeted the alanine moiety of Ala-tRNAPro. The importance of the CCA76 end of the tRNA for deacylation activity and key amino acid residues in HsProX for its editing function were also identified.

Histidyl-tRNA Synthetase

1999 ◽  
Vol 380 (6) ◽  
Author(s):  
W. Freist ◽  
J.F. Verhey ◽  
A. Rühlmann ◽  
D.H. Gauss ◽  
J.G. Arnez
Keyword(s):  
Amino Acid ◽  
Cell Metabolism ◽  
Trna Synthetase ◽  
Side Chain ◽  
Amino Acid Residues ◽  
Rheumatic Arthritis ◽  
Short Chain Length ◽  
Trna Synthetases ◽  
Catalytic Functions ◽  
Step Mechanism

AbstractHistidyl-tRNA synthetase (HisRS) is responsible for the synthesis of histidyl-transfer RNA, which is essential for the incorporation of histidine into proteins. This amino acid has uniquely moderate basic properties and is an important group in many catalytic functions of enzymes.A compilation of currently known primary structures of HisRS shows that the subunits of these homodimeric enzymes consist of 420–550 amino acid residues. This represents a relatively short chain length among aminoacyl-tRNA synthetases (aaRS), whose peptide chain sizes range from about 300 to 1100 amino acid residues.The crystal structures of HisRS from two organisms and their complexes with histidine, histidyl-adenylate and histidinol with ATP have been solved. HisRS fromThe aminoacylation reaction follows the standard two-step mechanism. HisRS also belongs to the group of aaRS that can rapidly synthesize diadenosine tetraphosphate, a compound that is suspected to be involved in several regulatory mechanisms of cell metabolism. Many analogs of histidine have been tested for their properties as substrates or inhibitors of HisRS, leading to the elucidation of structure-activity relationships concerning configuration, importance of the carboxy and amino group, and the nature of the side chain.HisRS has been found to act as a particularly important antigen in autoimmune diseases such as rheumatic arthritis or myositis. Successful attempts have been made to identify epitopes responsible for the complexation with such auto-antibodies.

scholarly journals Synthetic Microcin C Analogs Targeting Different Aminoacyl-tRNA Synthetases

2009 ◽  
Vol 191 (20) ◽  
pp. 6273-6280 ◽  
Author(s):  
Pieter Van de Vijver ◽  
Gaston H. M. Vondenhoff ◽  
Teymur S. Kazakov ◽  
Ekaterina Semenova ◽  
Konstantin Kuznedelov ◽  
...  
Keyword(s):  
Amino Acid ◽  
Chemical Synthesis ◽  
Antibacterial Agent ◽  
Trna Synthetase ◽  
Trojan Horse ◽  
Amino Acid Substitutions ◽  
Carboxyl Group ◽  
Antibacterial Compounds ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases

ABSTRACT Microcin C (McC) is a potent antibacterial agent produced by some strains of E scherichia coli. McC consists of a ribosomally synthesized heptapeptide with a modified AMP attached through a phosphoramidate linkage to the α-carboxyl group of the terminal aspartate. McC is a Trojan horse inhibitor: it is actively taken inside sensitive cells and processed there, and the product of processing, a nonhydrolyzable aspartyl-adenylate, inhibits translation by preventing aminoacylation of tRNAAsp by aspartyl-tRNA synthetase (AspRS). Changing the last residue of the McC peptide should result in antibacterial compounds with targets other than AspRS. However, mutations that introduce amino acid substitutions in the last position of the McC peptide abolish McC production. Here, we report total chemical synthesis of three McC-like compounds containing a terminal aspartate, glutamate, or leucine attached to adenosine through a nonhydrolyzable sulfamoyl bond. We show that all three compounds function in a manner similar to that of McC, but the first compound inhibits bacterial growth by targeting AspRS while the latter two inhibit, respectively, GluRS and LeuRS. Our approach opens a way for creation of new antibacterial Trojan horse agents that target any 1 of the 20 tRNA synthetases in the cell.

scholarly journals Structural Basis for the Recognition of Isoleucyl-Adenylate and an Antibiotic, Mupirocin, by Isoleucyl-tRNA Synthetase

2001 ◽  
Vol 276 (50) ◽  
pp. 47387-47393 ◽  
Author(s):  
Takashi Nakama ◽  
Osamu Nureki ◽  
Shigeyuki Yokoyama
Keyword(s):  
Amino Acid ◽  
Thermus Thermophilus ◽  
High Energy ◽  
Trna Synthetase ◽  
Structural Basis ◽  
Amino Acid Residues ◽  
Trna Synthetases ◽  
Chemical Structures ◽  
Aminoacyl Trna Synthetases ◽  
The Common

An analogue of isoleucyl-adenylate (Ile-AMS) potently inhibits the isoleucyl-tRNA synthetases (IleRSs) from the three primary kingdoms, whereas the antibiotic mupirocin inhibits only the eubacterial and archaeal IleRSs, but not the eukaryotic enzymes, and therefore is clinically used against methicillin-resistantStaphylococcus aureus. We determined the crystal structures of the IleRS from the thermophilic eubacterium,Thermus thermophilus, in complexes with Ile-AMS and mupirocin at 3.0- and 2.5-Å resolutions, respectively. A structural comparison of the IleRS·Ile-AMS complex with the adenylate complexes of other aminoacyl-tRNA synthetases revealed the common recognition mode of aminoacyl-adenylate by the class I aminoacyl-tRNA synthetases. The Ile-AMS and mupirocin, which have significantly different chemical structures, are recognized by many of the same amino acid residues of the IleRS, suggesting that the antibiotic inhibits the enzymatic activity by blocking the binding site of the high energy intermediate, Ile-AMP. In contrast, the two amino acid residues that concomitantly recognize Ile-AMS and mupirocin are different between the eubacterial/archaeal IleRSs and the eukaryotic IleRSs. Mutagenic analyses revealed that the replacement of the two residues significantly changed the sensitivity to mupirocin.

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