title: Toward understanding phosphoseryl-tRNACys formation: the crystal structure of Methanococcus maripaludis phosphoseryl-tRNA synthetase.
abstract: A number of archaeal organisms generate Cys-tRNA(Cys) in a two-step pathway, first charging phosphoserine (Sep) onto tRNA(Cys) and subsequently converting it to Cys-tRNA(Cys). We have determined, at 3.2-A resolution, the structure of the Methanococcus maripaludis phosphoseryl-tRNA synthetase (SepRS), which catalyzes the first step of this pathway. The structure shows that SepRS is a class II, alpha(4) synthetase whose quaternary structure arrangement of subunits closely resembles that of the heterotetrameric (alphabeta)(2) phenylalanyl-tRNA synthetase (PheRS). Homology modeling of a tRNA complex indicates that, in contrast to PheRS, a single monomer in the SepRS tetramer may recognize both the acceptor terminus and anticodon of a tRNA substrate. Using a complex with tungstate as a marker for the position of the phosphate moiety of Sep, we suggest that SepRS and PheRS bind their respective amino acid substrates in dissimilar orientations by using different residues.
authors.affiliation: Department of Molecular Biophysics and Biochemistry and Chemistry and Howard Hughes Medical Institute, Yale University, New Haven, CT 06520-8114, USA.
authors.forename: Satwik
authors.initials: S
authors.lastname: Kamtekar
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hohn
authors.forename: Hee-Sung
authors.initials: HS
authors.lastname: Park
authors.forename: Michael
authors.initials: M
authors.lastname: Schnitzbauer
authors.forename: Anselm
authors.initials: A
authors.lastname: Sauerwald
authors.forename: Dieter
authors.initials: D
authors.lastname: Söll
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Steitz
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D011756:Diphosphates / Q000378:metabolism; D007700:Kinetics; D017017:Methanococcus / Q000737:chemistry* / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry; D010768:Phosphoserine / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012350:RNA, Transfer, Cys / Q000096:biosynthesis*; D040681:Structural Homology, Protein; D016963:Thermus thermophilus / Q000201:enzymology
chemical_list: D011756:Diphosphates; D050505:Mutant Proteins; D012350:RNA, Transfer, Cys; D010768:Phosphoserine; D000255:Adenosine Triphosphate; D000604:Amino Acyl-tRNA Synthetases