Gnat

Abstract: ▪ Abstract Hundreds of acetyltransferases exist. All use a common acetyl donor—acetyl coenzyme A—and each exhibits remarkable specificity for acetyl acceptors, which include small molecules and proteins. Analysis of the primary sequences of these enzymes indicates that they can be sorted into several superfamilies. This review covers the three-dimensional structures of members of one of these superfamilies, now referred to in the literature as the GCN5-related N-acetyltransferases (GNAT), reflecting the importance of one functional category, the histone acetyltransferases. Despite the diversity of substrate specificities, members of the GNAT superfamily demonstrate remarkable similarity in protein topology and mode of acetyl coenzyme A binding, likely reflecting a conserved catalytic mechanism.

Abstract: The GCN5-related N-acetyltransferases family (GNAT) is an important family of proteins that includes more than 100000 members among eukaryotes and prokaryotes. Acetylation appears as a major regulatory post-translational modification and is as widespread as phosphorylation. N-Acetyltransferases transfer an acetyl group from acetyl-CoA to a large array of substrates, from small molecules such as aminoglycoside antibiotics to macromolecules. Acetylation of proteins can occur at two different positions, either at the amino-terminal end (αN-acetylation) or at the e-amino group (eN-acetylation) of an internal lysine residue. GNAT members have been classified into different groups on the basis of their substrate specificity, and in spite of a very low primary sequence identity, GNAT proteins display a common and conserved fold. This Current Topic reviews the different classes of bacterial GNAT proteins, their functions, their structural characteristics, and their mechanism of action.

Abstract: General control non-repressible 5 (GCN5)-related N-acetyltransferases (GNAT) catalyze the transfer of an acyl moiety from acyl coenzyme A (acyl-CoA) to a diverse group of substrates and are widely distributed in all domains of life. This review of the currently available data acquired on GNAT enzymes by a combination of structural, mutagenesis and kinetic methods summarizes the key similarities and differences between several distinctly different families within the GNAT superfamily, with an emphasis on the mechanistic insights obtained from the analysis of the complexes with substrates or inhibitors. It discusses the structural basis for the common acetyltransferase mechanism, outlines the factors important for the substrate recognition, and describes the mechanism of action of inhibitors of these enzymes. It is anticipated that understanding of the structural basis behind the reaction and substrate specificity of the enzymes from this superfamily can be exploited in the development of novel therapeutics to treat human diseases and combat emerging multidrug-resistant microbial infections.

Abstract: Motivation: Text mining in the biomedical domain aims at helping researchers to access information contained in scientific publications in a faster, easier and more complete way. One step towards this aim is the recognition of named entities and their subsequent normalization to database identifiers. Normalization helps to link objects of potential interest, such as genes, to detailed information not contained in a publication; it is also key for integrating different knowledge sources. From an information retrieval perspective, normalization facilitates indexing and querying. Gene mention normalization (GN) is particularly challenging given the high ambiguity of gene names: they refer to orthologous or entirely different genes, are named after phenotypes and other biomedical terms, or they resemble common English words. Results: We present the first publicly available system, GNAT, reported to handle inter-species GN. Our method uses extensive background knowledge on genes to resolve ambiguous names to EntrezGene identifiers. It performs comparably to single-species approaches proposed by us and others. On a benchmark set derived from BioCreative 1 and 2 data that contains genes from 13 species, GNAT achieves an F-measure of 81.4% (90.8% precision at 73.8% recall). For the single-species task, we report an F-measure of 85.4% on human genes. Availability: A web-frontend is available at http://cbioc.eas.asu.edu/gnat/. GNAT will also be available within the BioCreative MetaService project, see http://bcms.bioinfo.cnio.es. Contact: joerg.hakenberg@asu.edu Supplementary information: The test data set, lexica, and links to external data are available at http://cbioc.eas.asu.edu/gnat/