Disease relevance of GLB1

• Overexpression of a class 1 Hb (GLB1) protects Arabidopsis thaliana plants from the effects of severe hypoxia [1].
• Each plant PII-like protein has high overall identity to E. coli PII (50%) [2].
• This observation is reminiscent of the role of PII in the regulation of NO (2) (-) metabolism in cyanobacteria [3].
• In enteric bacteria PII is uridylylated on a specific tyrosine residue in the T-loop region, while in certain cyanobacteria it is phosphorylated at the serine residue two positions away from the equivalent modified tyrosine of enteric bacteria [4].

High impact information on GLB1

• The PII signal transduction protein of Arabidopsis thaliana forms an arginine-regulated complex with plastid N-acetyl glutamate kinase [5].
• Enzyme kinetic analysis showed that PII increases N-acetyl glutamate kinase activity slightly, but the primary function of binding is to relieve inhibition of enzyme activity by the pathway product, arginine [5].
• In eukaryotes, PII has only been identified in red algae and plants, and in these organisms, PII localizes to the plastid [5].
• Structures of PII also reveal how citrate and malonate bind near the triphosphate binding site occupied by ATP in bacterial and archaeal PII proteins [6].
• The 1.9 A resolution crystal structure of PII from Arabidopsis thaliana reveals for the first time the molecular structure of a widely conserved regulator of carbon and nitrogen metabolism from a eukaryote [6].

Biological context of GLB1

• They did not display an altered growth or developmental phenotype when grown under non-limiting conditions suggesting that the PII protein does not play a crucial role in plants [3].
• All results indicate that plant PII is not regulated by phosphorylation [4].

Associations of GLB1 with chemical compounds

• The major PII-interacting protein is the chloroplast-localized enzyme N-acetyl glutamate kinase, which catalyzes the key regulatory step in the pathway to arginine biosynthesis [5].
• However, in vitro grown PII mutants did show a higher sensitivity to nitrite (NO (2) (-) ) compared to the wild-type plants [3].

Regulatory relationships of GLB1

• Interactions between PII and NAGK appear to limit the degree of opening and closing of the active-site cleft in opposition to a domain-separating inhibitory effect exerted by arginine, thus explaining the stimulatory effect of PII on the kinetics of arginine-inhibited NAGK [7].

Analytical, diagnostic and therapeutic context of GLB1

• We have used affinity chromatography and mass spectrometry to identify the PII-binding proteins of Arabidopsis thaliana [5].
• The interaction of PII with N-acetyl glutamate kinase was confirmed through pull-down, gel filtration, and isothermal titration calorimetry experiments, and binding was shown to be enhanced in the presence of the downstream product, arginine [5].
• Western blot analyses reveal that the plant PII-like protein is a nuclear-encoded chloroplast protein [2].
• Using Arabidopsis transcriptome microarray (CATMA) and RT-PCR analyses, it was found that none of the genes involved in the arginine biosynthetic or catabolic pathways were differentially expressed in a PII knock-out mutant background [8].

References