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INTRODUCTIONScope Aminoacyl-tRNA synthetases are a group of enzymes that ensure the fidelity of transfer of genetic information from the DNA into the protein [1]. They are found in all living organisms, and their key mode of action is graphically depicted in Figure 1.  Figure 1. Key activities of aminoacyl-tRNA synthetases. The enzyme first catalysis the reaction between a given aminoacid (AA) and ATP forming aminoacyl-AMP. Then the aminoacyl moiety is transferred to tRNA. The final product i.e. aminoacyl-tRNA is further utilized in protein synthesis. As these enzymes are crucial for living organisms they constitute an appealing molecular target for drug design for compounds active against pathogenic bacteria. The exploitation of differences between the enzymes of procariotic and eucariotic organisms may lead to discoveries of new drugs. Thus it is important to collect compounds that are known to inhibit enzymatic activities of aminoacyl-tRNA synthetases. Methods We searched for known inhibitors of aminoacyl-tRNA synthetases in articles published from 2001 to 2006, found by PubMed search engine. Reviews published before 2001 were also taken into account in creation of the database of inhibitors of aminoacyl-tRNA synthetases. Molecules 0000-0239 were obtained from the References [2-23]. Next Marvin applets were used to create files with 3D structures of these compounds in 'mol' format and to convert structures between different file types. Two conformations were chosen for each molecule. The conformation A is the one of the lowest energy in Marvin's optimization with Dreiding force field [24]. The conformation B is the conformation whose RMSD (root mean square deviation) from the conformer A is the largest in the set of conformations generated by Marvin's molconvert utility. Application The presented database is composed of 240 molecules known from literature to inhibit enzymatic activity of aminoacyl-tRNA synthetases. The geometries of all these 240 molecules are available in two different conformations. Moreover the database is equiped with a search engine to search for molecules having desired functional groups, i.e. possessing a given smile's substring. The 3D geometries of ligands can be used directly for various computational tests including the search for potential inhibitors in molecular docking or virtual high throughput screening experiments. If you find the presented dataset of ligands of aminoacyl-tRNA synthetases useful in your studies please cite: M. Torchala, M. Hoffmann, "IA, database of known ligands of aminoacyl-tRNA synthetases", J. Comp-Aid. Mol. Des. 21, 523-525 (2007). |