Towards structural understanding of feedback control of arginine biosynthesis: cloning and expression of the gene for the arginine-inhibited N-acetyl-L-glutamate kinase from Pseudomonas aeruginosa, purification and crystallization of the recombinant enzyme and preliminary X-ray studies

Acta Crystallogr D Biol Crystallogr. 2002 Jun;58(Pt 6 Pt 2):1045-7. doi: 10.1107/s0907444902005243. Epub 2002 May 29.

Abstract

N-Acetyl-L-glutamate kinase (NAGK) catalyzes the second step in the pathway of arginine biosynthesis in microorganisms and plants. In many species, it is the pathway-controlling enzyme and is subject to feedback inhibition by arginine. The gene for the best characterized arginine-inhibitable NAGK, that from Pseudomonas aeruginosa, has been cloned in a pET22 plasmid and overexpressed in Escherichia coli. The enzyme was purified in three steps to 95% purity and was shown by cross-linking to form dimers. It was crystallized by the hanging-drop vapour-diffusion method at 277 K in the presence of ADP, Mg and N-acetyl-L-glutamate. The crystallization solution contained 0.1 M sodium cacodylate pH 6.5, 150-170 mM magnesium acetate and 13% polyethylene glycol 8000. Prismatic crystals of maximum dimension approximately 0.5 mm diffract to 2.75 A resolution and belong to space group P1 (unit-cell parameters a = 71.86, b = 98.78, c = 162.9 A, alpha = 91.49, beta = 92.03, gamma = 107.56 degrees ). Packing density considerations agree with 6-18 NAGK monomers in the asymmetric unit, with a corresponding solvent content of 79-36%. Self-rotation function calculations confirm the space group and suggest the presence of 3-7 dimers in the unit cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / biosynthesis*
  • Cloning, Molecular
  • Crystallization
  • Crystallography, X-Ray
  • Electrophoresis, Polyacrylamide Gel
  • Feedback, Physiological
  • Phosphotransferases (Carboxyl Group Acceptor) / antagonists & inhibitors
  • Phosphotransferases (Carboxyl Group Acceptor) / chemistry*
  • Phosphotransferases (Carboxyl Group Acceptor) / isolation & purification
  • Protein Conformation
  • Pseudomonas aeruginosa / enzymology*
  • Recombinant Proteins / chemistry

Substances

  • Recombinant Proteins
  • Arginine
  • Phosphotransferases (Carboxyl Group Acceptor)
  • acetylglutamate kinase