2RD5

Structural Basis for the Regulation of N-Acetylglutamate Kinase by PII in Arabidopsis thaliana.

(2007) J Biol Chem 282: 35733-35740

• PubMed: 17913711 Search on PubMed
• DOI: https://doi.org/10.1074/jbc.M707127200
• Primary Citation of Related Structures:  
  2RD5


• PubMed Abstract: 
  

  PII is a highly conserved regulatory protein found in organisms across the three domains of life. In cyanobacteria and plants, PII relieves the feedback inhibition of the rate-limiting step in arginine biosynthesis catalyzed by N-acetylglutamate kinase (NAGK). To understand the molecular structural basis of enzyme regulation by PII, we have determined a 2.5-A resolution crystal structure of a complex formed between two homotrimers of PII and a single hexamer of NAGK from Arabidopsis thaliana bound to the metabolites N-acetylglutamate, ADP, ATP, and arginine. In PII, the T-loop and Trp(22) at the start of the alpha1-helix, which are both adjacent to the ATP-binding site of PII, contact two beta-strands as well as the ends of two central helices (alphaE and alphaG) in NAGK, the opposing ends of which form major portions of the ATP and N-acetylglutamate substrate-binding sites. The binding of Mg(2+).ATP to PII stabilizes a conformation of the T-loop that favors interactions with both open and closed conformations of NAGK. 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.

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Organizational Affiliation: 

Department of Biological Sciences and the Alberta Ingenuity Centre for Carbohydrate Science, University of Calgary, Calgary, Alberta T2N 1N4, Canada.