title: Novel and unique domains in aminoacyl-tRNA synthetases from human fungal pathogens Aspergillus niger, Candida albicans and Cryptococcus neoformans.
abstract: BACKGROUND
  Some species of fungi can cause serious human diseases, particularly to immuno-compromised individuals. Opportunistic fungal infections are a leading cause of mortality, and present an emerging challenge that requires development of new and effective therapeutics. Aminoacyl-tRNA synthetases (aaRSs) are indispensable components of cellular protein translation machinery and can be targeted for discovery of novel anti-fungal agents.
  
  
  RESULTS
  Validation of aaRSs as potential drug targets in pathogenic microbes prompted us to investigate the genomic distribution of aaRSs within three fungi that infect humans - A. niger, C. albicans and C. neoformans. Hidden Markov Models were built for aaRSs and related proteins to search for homologues in these fungal genomes. Here, we provide a detailed and comprehensive annotation for 3 fungal genome aaRSs and their associated proteins. We delineate predicted localizations, subdomain architectures and prevalence of unusual motifs within these aaRSs. Several fungal aaRSs have unique domain appendages of unknown function e.g. A. niger AsxRS and C. neoformans TyrRS have additional domains that are absent from human homologs.
  
  
  CONCLUSIONS
  Detailed comparisons of fungal aaRSs with human homologs suggest key differences that could be exploited for specific drug targeting. Our cataloging and structural analyses provide a comprehensive foundation for experimentally dissecting fungal aaRSs that may enable development of new anti-fungal agents.
authors.forename: Manish
authors.initials: M
authors.lastname: Datt
authors.affiliation: Structural and Computational Biology group, International Center for Genetic Engineering and Biotechnology (ICGEB), New Delhi 110067, India. amit.icgeb@gmail.com.
authors.forename: Amit
authors.initials: A
authors.lastname: Sharma
mesh_terms: D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D001234:Aspergillus niger / Q000235:genetics* / Q000378:metabolism; D002176:Candida albicans / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology; D003455:Cryptococcus neoformans / Q000235:genetics* / Q000378:metabolism; D066264:Datasets as Topic; D016681:Genome, Fungal; D006801:Humans; D008390:Markov Chains; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D021381:Protein Transport; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D000604:Amino Acyl-tRNA Synthetases