| Nucleic Acids Research | Pages |
The Aminoacyl-tRNA Synthetase Data Bank (AARSDB)
Introduction
Description Of The Database
Availability Of The Database
Acknowledgement
References
The Aminoacyl-tRNA Synthetase Data Bank (AARSDB)
ABSTRACT
INTRODUCTION
The universal genetic code is established in a single biochemical reaction-the aminoacylation of transfer ribonucleic acids (tRNAs). The reaction is carried out by aminoacyl-tRNA synthetases (AARS). Aminoacyl-tRNA synthetases are, in fact, the only components of the gene expression machinery that function on the interface between the nucleic acids and proteins. There are three particularly interesting aspects of AARSs research. First, the mechanism of amino acid recognition and activation, second, the specificity of tRNA recognition and third, their origin and evolution (1). The synthetases constitute a family of 20 enzymes that are responsible for the specific esterification of tRNAs with their cognate amino acids, and thus are essential in maintaining the fidelity of the protein biosynthesis process. In Prokaryota there are some deviations of this number which include doubling of some AARSs genes, post-aminoacylation recharging of aa-tRNA as an alternative decoding mechanism and finally lack of at least one gene encoding AARS, e.g., three in Methanoccocus jannaschii (2). In contrast, all eukaryotes have a full set of AARS genes.
The aminoacylation reaction is achieved in two steps (Fig.
The fidelity of the aminoacylation reaction is controlled by the positive and negative regulatory elements in tRNAs and AARS which permit both recognition and productive binding of cognate pairs as well as discrimination against a non-productive binding of non-cognate pairs. The accuracy of this process is at least 10 000:1, and constitutes one of the fundamental problems in molecular recognition (3,4).
Figure 1. Two steps of an aminoacyl-tRNA formation catalysed by AARSs. Ensuring the accurate flow of genetic information in the processes of DNA replication and protein biosynthesis is beyond the limits of conventional specificity. There is a need for additional proofreading mechanisms operating at several levels. Such mechanisms control the fidelity of DNA and RNA synthesis and the aminoacylation reaction. The need for proofreading is evident in the case of AARSs that have isosteric or smaller competing substrates. One of the strongest components determining the specificity is steric repulsion. A smaller substrate can always rattle around in a larger cavity and also it is energetically unfavourable to cram a larger substrate into the active site built for smaller one. The active site of AARS acts as a coarse sieve, allowing activation at a substantial rate only those amino acids that are of the same size or smaller than the desired one. The active site responsible for the hydrolysis of the aminoacyl-adenylate is the fine sieve that destroys the products of the activation of amino acids smaller than the correct ones (5). Recently the idea of `double sieve' mechanism for proofreading (editing) has been confirmed by solving the crystal structure of isoleucyl-tRNA synthetase from Thermus thermophilus (6). In spite of their common catalytic function, the AARSs have long been known to differ in the size, amino acid sequences and subunit structure. The quaternary structures of synthetases include monomers ([alpha]), homodimers and tetramers ([alpha]2, [alpha]4) and heterotetramers ([alpha]2[beta]2). The peptide size of the subunits in Escherichia coli varies from 344 aa for TrpRS to 951 for ValRS. The eukaryotic enzymes are usually larger than their prokaryotic counterparts. This is due to the presence of C- and N-terminal extensions that are dispensable for the aminoacylation, but their function is still unclear (7,8). Although AARSs catalyse the same basic reaction and share a common substrate (ATP) and cofactor (magnesium), they form a quite diverse group of enzymes. On the other hand, amino acids share common core structure and tRNAs have the same basic fold, that allows them to be recognized by other components of the protein biosynthesis pathway. The amino acids are attached to the same 3[prime]-end of tRNA. Structural and sequence analyses of all AARSs clearly shows, that there are two exclusive classes (class I and class II) of enzymes. This shows that two distinct structural frameworks evolved independently to perform the aminoacylation reaction. The catalytic domain of class I enzymes is formed by the so-called Rossmann fold, first recognised as a nucleotide binding element. On the other hand, class II enzymes have a novel antiparallel fold that was identified for the first time in the structure of SerRS (7,9). Apart from the different ATP-binding motifs, the two classes of synthetases differ in their mode of tRNA binding. The crystallographic studies of AARSs in free and complexed forms allow us to gain insight into the specificity of substrate recognition and the catalysis itself (7). In contrast to prokaryotic synthetases, the eukaryotic enzymes are often found to be involved in forming supracomplexes through self-assembly or association with other protein synthesis machinery components and cellular structures (10). They are often components of multisynthetase complexes, that also include several proteins of unknown function (11). The exact structure and composition of these complexes is controversial. Different forms have been isolated, depending on the purification method (10). The understanding of the structure of these multienzymatic complexes is important to find the functional link between the aminoacylation and other cellular processes. In addition to the aminoacylation reaction, some AARSs have been also found to be involved in other cellular processes. Glycyl-tRNA synthetase has been shown to be responsible for the synthesis and turnover of diadenosine tetraphosphate (Ap4A) that plays an important role in a response of bacterial and eukaryotic cells to a variety of stress conditions (12,13). The diadenosine oligophosphates [Ap(n)A] including Ap4A have been recently shown to function as a new class of signalling molecules within the cell (14,15). Mitochondrial TyrRS from Neurospora crassa has been shown to be a key component for the splicing of group I intron of pre-rRNA, by substitution of the missing RNA domain of this otherwise self-splicing intron (16). In some instances, the AARSs are involved in autoregulation of their expression on the translation level, by binding the tRNA-like structures within the mRNA (17).Several AARSs have been found to be autoantigens for a subgroup of patients with the idiopathic inflammatory myopathies, polymyositis and dermatomyositis (18). Autoantibodies against synthetases are found almost exclusively in these cases, with patients having antibodies generally against only one synthetase. Most commonly, the antibodies are directed against HisRS, labelled `anti-Jo-1' autoantibodies, but the antibodies to threonyl-, alanyl- or glycyl-tRNA synthetases or the multienzymatic complex have also been found (18). Table 1. Recently, a subset of familial and sporadic amyotrophic lateral sclerosis cases have been found to be associated with mutations in the gene encoding Cu, Zn superoxide dismutase (SOD1), that binds lysyl-tRNA synthetase (19).
DESCRIPTION OF THE DATABASE
Table 2. Table 3. The AARS Database is a collection of amino acid sequences of all AARSs published to date (August 1998). The database entries are based on the EMBL/SWISS-PROT format (Table 1). In addition to the amino acid sequences, they include SWISS-PROT sequence name and accession number, short description of the sequence, organism name and its taxonomic classification, as well as basic bibliographic information. Since most of the AARS primary structures were determined on the nucleic acid level the appropriate accession numbers of the related entries in nucleotide sequences databases (EMBL/GenBank, TIGR) are also included. The availability of 3D structural data is indicated by cross-references to the Brookhaven Protein Data Base. The data included in the AARS database also contain partial sequences that might be useful for some comparative and evolutionary studies. According to the original SWISS-PROT description, some of the entries have been marked as putative or probable. Currently the database contains 423 amino acid sequences of cytoplasmic and organelle synthetases from a variety of organisms. The summary of the database content, showing the numbers of primary structures for given amino acid specificity is presented in Table 2.
Most of the data in the database come from genome sequencing projects. It is interesting to note that in some cases the genes encoding some of the AARS have not been identified in the whole genomes. The best example is a genome of M.jannaschii, in which only 17 AARS genes have been identified so far. The summary of synthetases found in some of the sequenced prokaryotic chromosomes is presented in Table 3.
AVAILABILITY OF THE DATABASE
The Aminoacyl-tRNA Synthetase Database can be accessed on the World Wide Web at the URL http://rose.man.poznan.pl/aars/index.html . To make the retrieval of the data as quick as possible, each individual sequence in the database is stored as a separate file. The sequences are grouped according to the AARS amino acid specificity or organism.
Any comments or suggestions concerning the database are welcome. Please contact us via Email at: jbarcisz{at}ibch.poznan.pl (Jan Barciszewski) or mszyman{at}ibch.poznan.pl(Maciej Szymanski).
ACKNOWLEDGEMENT
This work was supported by a grant from the Polish State Committee for Scientific Research.
REFERENCES
This article has been cited by other articles:
This page is run by Oxford University Press, Great Clarendon Street, Oxford OX2 6DP, as part of the OUP Journals
Comments and feedback: www-admin{at}oup.co.uk
Last modification: 9 Dec 1998
Copyright©Oxford University Press, 1998.
CiteULike 
Connotea 
Del.icio.us What's this?
M. Szymanski and J. Barciszewski
Aminoacyl-tRNA synthetases database Y2K
Nucleic Acids Res.,
January 1, 2000;
28(1):
326 - 328.
[Abstract]
[Full Text]
[PDF]
This Article 
Abstract
Print PDF (75K)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Search for citing articles in:
ISI Web of Science (1)
Request Permissions
Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Articles by Szymanski, M.
Articles by Barciszewski, J.
Search for Related Content
PubMed
PubMed Citation
Articles by Szymanski, M.
Articles by Barciszewski, J.
Social Bookmarking
What's this?