Article
- The EMBO Journal (2001) 20, 6583 - 6590
- doi:10.1093/emboj/20.23.6583
V-shaped structure of glutamyl-tRNA reductase, the first enzyme of tRNA-dependent tetrapyrrole biosynthesis
Jürgen Moser1,4, Wolf-Dieter Schubert2,4, Viola Beier2, Ingo Bringemeier3, Dieter Jahn1 and Dirk W. Heinz2
- Institute of Microbiology, Technical University Braunschweig, Spielmannstrasse 7, D-38106 Braunschweig, Germany
- Department of Structural Biology, German Research Center for Biotechnology, Mascheroder Weg 1, D-38104 Braunschweig, Germany
- Microsoft Germany Inc., Germany
- J.Moser and W.D.Schubert contributed equally to this work
Correspondence to:
Dirk W. Heinz, E-mail: dih@gbf.de
Received 14 August 2001; Accepted 15 October 2001; Revised 12 October 2001
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 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.
Keywords:
- crystal structure,
- glutamyl-tRNA reductase,
- metabolic channeling,
- tetrapyrrole biosynthesis,
- tRNA
