title: V-shaped structure of glutamyl-tRNA reductase, the first enzyme of tRNA-dependent tetrapyrrole biosynthesis.
abstract: Processes vital to life such as respiration and photosynthesis critically depend on the availability of tetrapyrroles including hemes and chlorophylls. tRNA-dependent catalysis generally is associated with protein biosynthesis. An exception is the reduction of glutamyl-tRNA to glutamate-1-semialdehyde by the enzyme glutamyl-tRNA reductase. This reaction is the indispensable initiating step of tetrapyrrole biosynthesis in plants and most prokaryotes. The crystal structure of glutamyl-tRNA reductase from the archaeon Methanopyrus kandleri in complex with the substrate-like inhibitor glutamycin at 1.9 A resolution reveals an extended yet planar V-shaped dimer. The well defined interactions of the inhibitor with the active site support a thioester-mediated reduction process. Modeling the glutamyl-tRNA onto each monomer reveals an extensive protein-tRNA interface. We furthermore propose a model whereby the large void of glutamyl-tRNA reductase is occupied by glutamate-1-semialdehyde-1,2-mutase, the subsequent enzyme of this pathway, allowing for the efficient synthesis of 5-aminolevulinic acid, the common precursor of all tetrapyrroles.
authors.affiliation: Institute of Microbiology, Technical University Braunschweig, Spielmannstrasse 7, D-38106 Braunschweig, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Moser
authors.forename: W D
authors.initials: WD
authors.lastname: Schubert
authors.forename: V
authors.initials: V
authors.lastname: Beier
authors.forename: I
authors.initials: I
authors.lastname: Bringemeier
authors.forename: D
authors.initials: D
authors.lastname: Jahn
authors.forename: D W
authors.initials: DW
authors.lastname: Heinz
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000737:chemistry*; D000617:Aminoglycosides; D000622:Aminolevulinic Acid / Q000378:metabolism; D000626:Aminopeptidases; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001105:Archaea / Q000201:enzymology*; D001665:Binding Sites; D002384:Catalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D019281:Dimerization; D043384:Glutamyl Aminopeptidase; D019751:Intramolecular Transferases / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011758:Pyrroles / Q000737:chemistry* / Q000378:metabolism; D012343:RNA, Transfer / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D045725:Tetrapyrroles
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D011758:Pyrroles; D011994:Recombinant Proteins; D045725:Tetrapyrroles; C444059:glutamycin; D000622:Aminolevulinic Acid; D012343:RNA, Transfer; D000445:Aldehyde Oxidoreductases; C067282:glutamyl tRNA reductase; D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase; D019751:Intramolecular Transferases; C061049:glutamate-1-semialdehyde 2,1-aminomutase