Premium
V‐shaped structure of glutamyl‐tRNA reductase, the first enzyme of tRNA‐dependent tetrapyrrole biosynthesis
Author(s) -
Moser Jürgen,
Schubert WolfDieter,
Beier Viola,
Bringemeier Ingo,
Jahn Dieter,
Heinz Dirk W.
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.23.6583
Subject(s) - tetrapyrrole , biology , transfer rna , biochemistry , reductase , biosynthesis , enzyme , oxidoreductase , aminoacyl trna synthetase , stereochemistry , rna , chemistry , gene
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 Å 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.