Glutamate-5-kinase from Escherichia coli: gene cloning, overexpression, purification and crystallization of the recombinant enzyme and preliminary X-ray studies

Acta Crystallogr D Biol Crystallogr. 2004 Nov;60(Pt 11):2091-4. doi: 10.1107/S0907444904023972. Epub 2004 Oct 20.

Abstract

Glutamate-5-kinase (G5K) catalyzes the first step of proline (and, in mammals, ornithine) biosynthesis. It is a key regulatory point of these routes, since it is the subject of feedback allosteric inhibition by proline or ornithine. The Escherichia coli gene (proB) for G5K was cloned in pET22, overexpressed in E. coli, purified in a few steps in high yield to 95% homogeneity in the highly active proline-inhibitable form and was shown by cross-linking to be a tetramer. It was crystallized by the hanging-drop vapour-diffusion method at 294 K in the presence of ADP, MgCl(2) and L-glutamate using 1.6 M MgSO(4), 0.1 M KCl in 0.1 M MES pH 6.5 as the crystallization solution. The tetragonal bipyramid-shaped crystals diffracted to 2.5 A resolution using synchrotron radiation. The crystals belong to space group P4(1(3))2(1)2, with unit-cell parameters a = b = 101.1, c = 178.6 A, and contain two monomers in the asymmetric unit, with 58% solvent content.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cloning, Molecular
  • Crystallization
  • Crystallography, X-Ray
  • Escherichia coli / enzymology*
  • Escherichia coli / genetics
  • Gene Expression
  • Genetic Vectors / genetics
  • Phosphotransferases (Carboxyl Group Acceptor) / biosynthesis
  • Phosphotransferases (Carboxyl Group Acceptor) / chemistry*
  • Phosphotransferases (Carboxyl Group Acceptor) / genetics
  • Phosphotransferases (Carboxyl Group Acceptor) / isolation & purification*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification

Substances

  • Recombinant Proteins
  • Phosphotransferases (Carboxyl Group Acceptor)
  • glutamate 5-kinase