Purification and side chain selective chemical modifications of glutamate dehydrogenase from Bacillus subtilis natto

Appl Biochem Biotechnol. 2014 Apr;172(7):3593-605. doi: 10.1007/s12010-014-0788-3. Epub 2014 Feb 21.

Abstract

Glutamate dehydrogenase (GDH) from Bacillus subtilis natto was purified to apparent homogeneity by ammonium sulfate precipitation, ion-exchange chromatography, size exclusion chromatography, and hydroxyapatite (HA) affinity chromatography. The GDH was purified 34-fold, with a yield of 41 % of total activity and a specific activity of 34.29 U/mg proteins. The molecular weight (Mr) of was measured at 47 kDa with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and 264 kDa with high-performance liquid chromatography (HPLC). The optimum pH and temperature for the deammoniation reaction were measured to be 7.5 and 30 °C, respectively. The active-site amino acid residues of GDH were investigated by chemical modification. The compounds 2,4,6-trinitrobenzenesulfonic acid (TNBS), phenylglyoxal (PG), and phenylmethanesulfonyl fluoride (PMSF) were used to modify lysine, arginine, and serine active site residues, respectively. After treatment with modifying reagents at concentrations of 1 mM, GDH activity fell to 10.7 % with TNBS, 83.3 % with PG, and 12.8 % with PMSF. However, with substrate protection, there was almost no loss in GDH activity following treatment with any modifying reagent. The kinetic parameters K m and V max were determined in each case. K m values for native GDH, 50 % TNBS-inactivated GDH, and 50 % PMSF-inactivated GDH were 0.037, 0.104, and 0.017 mM, respectively. V max values were 0.048, 0.022, and 0.031 mM/s, respectively. These results suggest that the active site contains one or more lysine residues that play a role in substrate binding and one or more serine residues that may maintain the enzyme conformation. However, arginine residues played less of a role in the activity of GDH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillus subtilis / chemistry
  • Bacillus subtilis / enzymology*
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / isolation & purification*
  • Bacterial Proteins / metabolism
  • Enzyme Stability
  • Glutamate Dehydrogenase / chemistry*
  • Glutamate Dehydrogenase / isolation & purification*
  • Glutamate Dehydrogenase / metabolism
  • Kinetics
  • Protein Conformation
  • Temperature

Substances

  • Bacterial Proteins
  • Glutamate Dehydrogenase