PDBsum entry: 1gpj

Reductase

PDB id: 1gpj

Contents

Protein chain

399 a.a. *

Ligands

GLU-GMC

CIT

Waters ×353

* Residue conservation analysis

PDB id:

1gpj

Name:

Reductase

Title:

Glutamyl-tRNA reductase from methanopyrus kandleri

Structure:

Glutamyl-tRNA reductase. Chain: a. Fragment: whole molecule, residues 1-404. Mutation: yes

Source:

Methanopyrus kandleri. Organism_taxid: 2320. Other_details: dsm 6324, german collection of microorganisms (dsm)

Biol. unit:

Dimer (from PDB file)

Resolution:

1.95Å R-factor: 0.212 R-free: 0.262

Authors:

J.Moser,W.-D.Schubert,V.Beier,I.Bringemeier,D.Jahn,D.W.Heinz

Key ref:

J.Moser et al. (2001). V-shaped structure of glutamyl-tRNA reductase, the first enzyme of tRNA-dependent tetrapyrrole biosynthesis. EMBO J, 20, 6583-6590. PubMed id: 11726494 DOI: 10.1093/emboj/20.23.6583

Date:

05-Nov-01 Release date: 04-Jan-02

Protein chain

Q9UXR8  (HEM1_METKA) -  Glutamyl-tRNA reductase

Seq: 404 a.a.

Struc: 399 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.1.2.1.70 - Glutamyl-tRNA reductase.
• Pathway: Porphyrin Biosynthesis (early stages)
• Reaction: L-glutamate 1-semialdehyde + NADP⁺ + tRNA(Glu) = L-glutamyl-tRNA(Glu) + NADPH

L-glutamate 1-semialdehyde (Bound ligand (Het Group name = GLU) corresponds exactly) + NADP(+) + tRNA(Glu) = L-glutamyl-tRNA(Glu) + NADPH

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Biological process: oxidation-reduction process (3 terms)
• Biochemical function: nucleotide binding (4 terms)

reference

DOI no: 10.1093/emboj/20.23.6583

EMBO J 20:6583-6590 (2001)

PubMed id: 11726494

V-shaped structure of glutamyl-tRNA reductase, the first enzyme of tRNA-dependent tetrapyrrole biosynthesis.

J.Moser, W.D.Schubert, V.Beier, I.Bringemeier, D.Jahn, D.W.Heinz.

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.

Selected figure(s)

Figure 2.
Figure 2 Structure of the GluTR dimer viewed (A) perpendicular to and (B) along the 2-fold axis. Monomers consist of three structural domains: (I) an N-terminal catalytic domain (blue); (II) an NAPDH-binding domain (green); and (III) a C-terminal dimerization domain (orange)--connected by an extended 18-turn 'spinal' -helix (dark-yellow). Glutamycin (red) binds at the catalytic domain. At the deep end of the large crevice between domains I and II a citrate anion (yellow) is bound. Figures 2, 3 and 5 were generated using MOLSCRIPT (Kraulis, 1991) rendered with RASTER3D (Merrit and Murphy, 1994).

Figure 6.
Figure 6 In the proposed complex GluTR -GSAM (blue/pink residues), the respective active sites are separated by 26 Å. GSA, the product of GluTR and the substrate of GSAM, would channel from GluTR to GSAM (green, dotted line). In GluTR, there is an opening immediately behind the central active site residue Arg50 surrounded by the loop residues Thr10 -Glu13, Glu93 -Ser94 and His84 blue asterisk). In the putative complex, this comes to lie opposite a partly disordered loop 159 -172 (Ser163 -Leu170 shown) proposed to be the active site entrance for GSAM (Hennig et al., 1997) and to be essential for catalysis (Contestabile et al., 2000). Gabaculine, an inhibitor of GSAM, indicates the position GSA presumably would occupy to initiate its conversion to ALA.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2001, 20, 6583-6590) copyright 2001.

Figures were selected by the author.