Predicted structure and fold recognition for the glutamyl tRNA reductase family of proteins

The conserved residues of glutamyl tRNA reductase (GTR) from Hordeum vulgare (GTRhorvu) were found from an alignment/pile-up of 24 homologous sequences found using BLAST searches. A multiple alignment of sequences was used to obtain a prediction of the secondary structure of the GTR's. This secondary structure was submitted to the THREADER program to find possible homologous 3D structures. To help select the template for predicting the fold for GTRhorvu, we employed both molecular-biological and biochemical information about GTRhorvu. After fitting the secondary structure of GTRhorvu to the selected template, the MODELLER program was used to determine the fold for GTRhorvu. This model was built using the B subunit of succinyl CoA synthetase, 1scuB, as a template for the 3D structure of GTRhorvu. From the predicted structure, possible regions were identified for the binding of glutamyl-tRNA, NADPH and a heme inhibitor. The predicted structure was used to propose a detailed biochemical mechanism for the GTR, involving Mg catalyzed thioester formation and reduction by NADPH to glutamate-1-semialdehyde. Sites for these reactions are identified. The predicted structure has been deposited in the Brookhaven database as ID 1b61.