title: Ligand co-crystallization of aminoacyl-tRNA synthetases from infectious disease organisms.
abstract: Aminoacyl-tRNA synthetases (aaRSs) charge tRNAs with their cognate amino acid, an essential precursor step to loading of charged tRNAs onto the ribosome and addition of the amino acid to the growing polypeptide chain during protein synthesis. Because of this important biological function, aminoacyl-tRNA synthetases have been the focus of anti-infective drug development efforts and two aaRS inhibitors have been approved as drugs. Several researchers in the scientific community requested aminoacyl-tRNA synthetases to be targeted in the Seattle Structural Genomics Center for Infectious Disease (SSGCID) structure determination pipeline. Here we investigate thirty-one aminoacyl-tRNA synthetases from infectious disease organisms by co-crystallization in the presence of their cognate amino acid, ATP, and/or inhibitors. Crystal structures were determined for a CysRS from Borrelia burgdorferi bound to AMP, GluRS from Borrelia burgdorferi and Burkholderia thailandensis bound to glutamic acid, a TrpRS from the eukaryotic pathogen Encephalitozoon cuniculi bound to tryptophan, a HisRS from Burkholderia thailandensis bound to histidine, and a LysRS from Burkholderia thailandensis bound to lysine. Thus, the presence of ligands may promote aaRS crystallization and structure determination. Comparison with homologous structures shows conformational flexibility that appears to be a recurring theme with this enzyme class.
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), Bethesda, MD, USA.|Beryllium Discovery Corp, Bainbridge Island, WA, 98110, USA.
authors.forename: Spencer O
authors.initials: SO
authors.lastname: Moen
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), Bethesda, MD, USA. tedwards@be4.com.|Beryllium Discovery Corp, Bainbridge Island, WA, 98110, USA. tedwards@be4.com.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Edwards
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), Bethesda, MD, USA.|Beryllium Discovery Corp, Bainbridge Island, WA, 98110, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Dranow
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), Bethesda, MD, USA.|Beryllium Discovery Corp, Bainbridge Island, WA, 98110, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Clifton
authors.affiliation: Berkeley Center for Structural Biology, Advanced Light Source, Berkeley, CA, 94720, USA.
authors.forename: Banumathi
authors.initials: B
authors.lastname: Sankaran
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), Bethesda, MD, USA.|University of Washington, Seattle, WA, 98195-6423, USA.
authors.forename: Wesley C
authors.initials: WC
authors.lastname: Van Voorhis
authors.affiliation: International Center for Genetic Engineering and Biotechnology, New Delhi, 110 067, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Sharma
authors.affiliation: University of Washington, Department of Genome Sciences, Seattle, WA, 98195-5065, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Manoil
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), Bethesda, MD, USA.|Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), Seattle, WA, 98109, USA.
authors.forename: Bart L
authors.initials: BL
authors.lastname: Staker
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), Bethesda, MD, USA.|Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), Seattle, WA, 98109, USA.|University of Washington, Department of Medical Education and Biomedical Informatics & Department of Global Health, Seattle, WA, 98195, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Myler
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), Bethesda, MD, USA.|Beryllium Discovery Corp, Bainbridge Island, WA, 98110, USA.
authors.forename: Donald D
authors.initials: DD
authors.lastname: Lorimer
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000201:enzymology*; D019117:Burkholderia / Q000201:enzymology*; D020134:Catalytic Domain; D003141:Communicable Diseases / Q000382:microbiology; D018360:Crystallography, X-Ray; D009670:Encephalitozoon cuniculi / Q000201:enzymology*; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D001426:Bacterial Proteins; D005656:Fungal Proteins; D008024:Ligands; D000604:Amino Acyl-tRNA Synthetases