Glu-256 is a main structural determinant for oligomerisation of human arginase I

FEBS Lett. 2001 Jul 20;501(2-3):161-5. doi: 10.1016/s0014-5793(01)02650-3.

Abstract

One determinant that could play a role in the quaternary structure of human arginase is the pair of salt links between the strictly conserved residues R255 from one monomer and E256 from every adjacent subunit. In this work, the ionic interaction between monomers was disrupted by expressing a human arginase where Glu-256 had been substituted by Gln. Biochemical analyses of the mutant protein showed that: (i) it shares the wild-type kinetic parameters of the arginine substrate; (ii) E256Q arginase behaves as a monomer by gel filtration; (iii) it is drastically inactivated by dialysis in the presence of EDTA, an inhibitory effect which is reversed by addition of Mn(2+); and (iv) the mutant enzyme loses thermal stability. The lack of oligomerisation for E256Q arginase and the conservation of E256 throughout evolution of the protein family suggest that this residue is involved in the quaternary structure of arginases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Arginase / chemistry*
  • Arginase / drug effects
  • Arginase / genetics
  • Arginase / metabolism
  • Edetic Acid / pharmacology
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Enzyme Stability
  • Glutamic Acid / chemistry*
  • Glutamic Acid / genetics
  • Glutamic Acid / metabolism
  • Humans
  • Kinetics
  • Manganese / pharmacology
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Polymers
  • Protein Structure, Quaternary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / drug effects
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Temperature

Substances

  • Enzyme Inhibitors
  • Polymers
  • Recombinant Proteins
  • Glutamic Acid
  • Manganese
  • Edetic Acid
  • Arginase