Structural Insights into the Second Step of RNA-dependent Cysteine Biosynthesis in Archaea: Crystal Structure of Sep-tRNA:Cys-tRNA Synthase from Archaeoglobus fulgidus

Ryuya Fukunaga, Shigeyuki Yokoyama

Research output: Contribution to journalArticle

Abstract

In the ancient organisms, methanogenic archaea, lacking the canonical cysteinyl-tRNA synthetase, Cys-tRNACys is produced by an indirect pathway, in which O-phosphoseryl-tRNA synthetase ligates O-phosphoserine (Sep) to tRNACys and Sep-tRNA:Cys-tRNA synthase (SepCysS) converts Sep-tRNACys to Cys-tRNACys. In this study, the crystal structure of SepCysS from Archaeoglobus fulgidus has been determined at 2.4 Å resolution. SepCysS forms a dimer, composed of monomers bearing large and small domains. The large domain harbors the seven-stranded β-sheet, which is typical of the pyridoxal 5′-phosphate (PLP)-dependent enzymes. In the active site, which is located near the dimer interface, PLP is covalently bound to the side-chain of the conserved Lys209. In the proximity of PLP, a sulfate ion is bound by the side-chains of the conserved Arg79, His103, and Tyr104 residues. The active site is located deep within the large, basic cleft to accommodate Sep-tRNACys. On the basis of the surface electrostatic potential, the amino acid residue conservation mapping, the position of the bound sulfate ion, and the substrate amino acid binding manner in other PLP-dependent enzymes, a binding model of Sep-tRNACys to SepCysS was constructed. One of the three strictly conserved Cys residues (Cys39, Cys42, or Cys247), of one subunit may play a crucial role in the catalysis in the active site of the other subunit.

Original languageEnglish (US)
Pages (from-to)128-141
Number of pages14
JournalJournal of molecular biology
Volume370
Issue number1
DOIs
StatePublished - Jun 29 2007
Externally publishedYes

Keywords

  • PLP
  • crystal structure
  • cysteine
  • phosphoserine
  • tRNA

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Structural Insights into the Second Step of RNA-dependent Cysteine Biosynthesis in Archaea: Crystal Structure of Sep-tRNA:Cys-tRNA Synthase from Archaeoglobus fulgidus'. Together they form a unique fingerprint.

  • Cite this