Structural highlights
Function
[HEM11_ARATH] Catalyzes the NADPH-dependent reduction of glutamyl-tRNA(Glu) to glutamate 1-semialdehyde (GSA). Probably involved in the tetrapyrrole synthesis required for the chlorophyll biosynthesis.[1] [2]
Publication Abstract from PubMed
Tetrapyrrole biosynthesis in plants, algae, and most bacteria starts from the NADPH-dependent reduction of glutamyl-tRNA by glutamyl-tRNA reductase (GluTR). The GluTR-catalyzed reaction is the rate-limiting step, and GluTR is the target of multiple posttranslational regulations, such as heme feedback inhibition, for the tetrapyrrole biosynthetic pathway. A recently identified GluTR regulator, GluTR binding protein (GluBP), has been shown to spatially organize tetrapyrrole synthesis by distributing GluTR into different suborganellar locations. Here we report the complex structure of GluTR-GluBP from Arabidopsis thaliana. The dimeric GluBP binds symmetrically to the catalytic domains of the V-shaped GluTR dimer via its C-terminal domain. A substantial conformational change of the GluTR NADPH-binding domain is observed, confirming the postulated rotation of the NADPH-binding domain for hydride transfer from NADPH to the substrate. Arg146, "guarding the door" for metabolic channeling, adopts alternative conformations, which may represent steps involved in substrate recognition and product release. A coupled enzyme assay shows that GluBP stimulates GluTR catalytic efficiency with an approximate threefold increase of the 5-aminolevulinic acid formation rate. In addition, the GluTR activity can be inhibited by heme in a concentration-dependent way regardless of the presence of GluBP. A structural alignment indicates that GluBP belongs to a heme-binding family involved in heme metabolism. We propose a catalytic mechanism model for GluTR, through which photosynthetic organisms can achieve precise regulation of tetrapyrrole biosynthesis.
Crystal structure of Arabidopsis glutamyl-tRNA reductase in complex with its stimulator protein.,Zhao A, Fang Y, Chen X, Zhao S, Dong W, Lin Y, Gong W, Liu L Proc Natl Acad Sci U S A. 2014 May 6;111(18):6630-5. doi:, 10.1073/pnas.1400166111. Epub 2014 Apr 21. PMID:24753615[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ilag LL, Kumar AM, Soll D. Light regulation of chlorophyll biosynthesis at the level of 5-aminolevulinate formation in Arabidopsis. Plant Cell. 1994 Feb;6(2):265-75. PMID:7908550 doi:http://dx.doi.org/10.1105/tpc.6.2.265
- ↑ Ujwal ML, McCormac AC, Goulding A, Kumar AM, Soll D, Terry MJ. Divergent regulation of the HEMA gene family encoding glutamyl-tRNA reductase in Arabidopsis thaliana: expression of HEMA2 is regulated by sugars, but is independent of light and plastid signalling. Plant Mol Biol. 2002 Sep;50(1):83-91. PMID:12139011
- ↑ Zhao A, Fang Y, Chen X, Zhao S, Dong W, Lin Y, Gong W, Liu L. Crystal structure of Arabidopsis glutamyl-tRNA reductase in complex with its stimulator protein. Proc Natl Acad Sci U S A. 2014 May 6;111(18):6630-5. doi:, 10.1073/pnas.1400166111. Epub 2014 Apr 21. PMID:24753615 doi:http://dx.doi.org/10.1073/pnas.1400166111
