Cofactors

There are no Cofactors for this Enzyme

Reaction Mechanism

glutamyl-tRNA reductase By Reference

Glutamyl-tRNA Reductase catalyses the reduction of the activated alpha-carboxyl group of glutamate from glutamyl-tRNA using NADPH to form glutamate-1-semialdehyde(GSA). GSA is then converted to 5-aminolevulenic acid, a precursor molecule for the biosynthesis of tetrapyrroles like chlorophylls, hemes and coenzyme B12.




• Summary
• Step 1
• Step 2
• Step 3
• Products

Cys48 acts as a nucleophile to attack the alpha-carboxyl group of glutamate, which is activated by an ester linkage to tRNA, forming a highly reactive enzyme-localised thioester and tRNA is released. Direct hydride transfer from NADPH, facilitated by His84, which acts as a base catalyst to stabilise the protonated tetrahedral intermediate, leads to the formation of the product GSA.

Catalytic Residues

AA	Uniprot	Uniprot Resid	PDB	PDB Resid
Cys	Q9UXR8	48	1gpj	48
His	Q9UXR8	84	1gpj	84

Step Components

intermediate formation, hydride transfer, enzyme-substrate complex formation, bimolecular nucleophilic addition, overall product formed, native state of enzyme regenerated, enzyme-substrate complex cleavage, overall reactant used, unimolecular elimination by the conjugate base, bimolecular nucleophilic substitution, aromatic unimolecular elimination by the conjugate base



Step 1.

The sulfryl group of Cys48 acts as a nucleophile to attack glutamate and the tRNA residue is eliminated. An enzyme thioester intermediate is formed.



Step 2.

A hydride is transferred from NADPH to the thioester intermediate. This is promoted by His84.



Step 3.

The tetrahedral intermediate collapses, releasing Cys48 and forming the product.



Products.

The products of the reaction.

View Reaction Mechanisms in M-CSA

Reaction Parameters

• Kinetic Parameters

  Organism	KM Value [mM]	Substrate	Comment
  Escherichia coli	0.039	NADPH	pH 8.1, 37°C

• Temperature

  There are no reaction parameters information for this Enzyme.

• pH

  There are no reaction parameters information for this Enzyme.

Associated Proteins

Citations

• Maintenance of heme homeostasis in Staphylococcus aureus through post-translational regulation of glutamyl-tRNA reductase.
• An alanine to valine mutation of glutamyl-tRNA reductase enhances 5-aminolevulinic acid synthesis in rice.
• The GluTR-binding protein is the heme-binding factor for feedback control of glutamyl-tRNA reductase.
• Fluorescence in blue light (FLU) is involved in inactivation and localization of glutamyl-tRNA reductase during light exposure.
• Controlled Partitioning of Glutamyl-tRNA Reductase in Stroma- and Membrane-Associated Fractions Affects the Synthesis of 5-Aminolevulinic Acid.
• Staphylococcus aureus HemX Modulates Glutamyl-tRNA Reductase Abundance To Regulate Heme Biosynthesis.
• Chloroplast SRP43 acts as a chaperone for glutamyl-tRNA reductase, the rate-limiting enzyme in tetrapyrrole biosynthesis.
• N-terminal engineering of glutamyl-tRNA reductase with positive charge arginine to increase 5-aminolevulinic acid biosynthesis.
• The Arabidopsis glutamyl-tRNA reductase (GluTR) forms a ternary complex with FLU and GluTR-binding protein.
• The Non-canonical Tetratricopeptide Repeat (TPR) Domain of Fluorescent (FLU) Mediates Complex Formation with Glutamyl-tRNA Reductase.
• Crystal structure of Arabidopsis glutamyl-tRNA reductase in complex with its stimulator protein.