title: Solution structure of Archaeglobus fulgidis peptidyl-tRNA hydrolase (Pth2) provides evidence for an extensive conserved family of Pth2 enzymes in archea, bacteria, and eukaryotes.
abstract: The solution structure of protein AF2095 from the thermophilic archaea Archaeglobus fulgidis, a 123-residue (13.6-kDa) protein, has been determined by NMR methods. The structure of AF2095 is comprised of four alpha-helices and a mixed beta-sheet consisting of four parallel and anti-parallel beta-strands, where the alpha-helices sandwich the beta-sheet. Sequence and structural comparison of AF2095 with proteins from Homo sapiens, Methanocaldococcus jannaschii, and Sulfolobus solfataricus reveals that AF2095 is a peptidyl-tRNA hydrolase (Pth2). This structural comparison also identifies putative catalytic residues and a tRNA interaction region for AF2095. The structure of AF2095 is also similar to the structure of protein TA0108 from archaea Thermoplasma acidophilum, which is deposited in the Protein Data Bank but not functionally annotated. The NMR structure of AF2095 has been further leveraged to obtain good-quality structural models for 55 other proteins. Although earlier studies have proposed that the Pth2 protein family is restricted to archeal and eukaryotic organisms, the similarity of the AF2095 structure to human Pth2, the conservation of key active-site residues, and the good quality of the resulting homology models demonstrate a large family of homologous Pth2 proteins that are conserved in eukaryotic, archaeal, and bacterial organisms, providing novel insights in the evolution of the Pth and Pth2 enzyme families.
authors.affiliation: Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, USA. rpowers3@unl.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Powers
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Mirkovic
authors.forename: Sharon
authors.initials: S
authors.lastname: Goldsmith-Fischman
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Acton
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Chiang
authors.forename: Yuanpeng J
authors.initials: YJ
authors.lastname: Huang
authors.forename: Lichung
authors.initials: L
authors.lastname: Ma
authors.forename: P K
authors.initials: PK
authors.lastname: Rajan
authors.forename: John R
authors.initials: JR
authors.lastname: Cort
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kennedy
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Liu
authors.forename: Burkhard
authors.initials: B
authors.lastname: Rost
authors.forename: Barry
authors.initials: B
authors.lastname: Honig
authors.forename: Diana
authors.initials: D
authors.lastname: Murray
authors.forename: Gaetano T
authors.initials: GT
authors.lastname: Montelione
mesh_terms: D001105:Archaea / Q000145:classification / Q000201:enzymology; D019843:Archaeal Proteins / Q000737:chemistry* / Q000145:classification*; D019611:Archaeoglobus fulgidus / Q000145:classification / Q000201:enzymology*; D001419:Bacteria / Q000145:classification / Q000201:enzymology; D001665:Binding Sites; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry* / Q000145:classification*; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D040681:Structural Homology, Protein
chemical_list: D019843:Archaeal Proteins; D012996:Solutions; D002265:Carboxylic Ester Hydrolases; C019674:aminoacyl-tRNA hydrolase