Purification and characterization of a metalloprotease from Chryseobacterium indologenes Ix9a and determination of the amino acid specificity with electrospray mass spectrometry

Protein Expr Purif. 1999 Apr;15(3):282-95. doi: 10.1006/prep.1998.1020.

Abstract

The heat-stable protease from Chryseobacterium indologenes Ix9a was purified to homogeneity using immobilized metal affinity chromatography. The enzyme was characterized as a metalloprotease with an approximate relative molecular mass of 24,000, a pH optimum of 6.5, and a high temperature optimum (50 degrees C). The metal chelator EDTA and the Zn2+-specific chelator 1,10-phenanthroline were identified as inhibitors and atomic absorption analysis showed that the enzyme contained Ca2+ and Zn2+. The activity of the apoenzyme could be restored with Ca2+, Zn2+, Mg2+, and Co2+. Phosphoramidon and Gly-d-Phe did not inhibit Chryseobacterium indologenes Ix9a protease. Heat inactivation did not follow first order kinetics, but showed biphasic inactivation curves. The protease has a Km of 0.813 microg. ml-1 for casein as substrate. Amino acid analysis showed that the protease contains a high amount of small amino acids like glycine, alanine, and serine, but a low concentration of methionine and no cysteine at all. Electrospray mass spectrometry of proteolysis fragments formed when insulin B chain was hydrolyzed showed cleavage at the amino terminal of leucine, tyrosine, and phenylalanine. A hydrophobic amino acid at the carboxyl donating side seems to increase the rate of reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acids
  • Apoenzymes / metabolism
  • Calcium / analysis
  • Cations, Divalent / pharmacology
  • Chromatography, Affinity
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme Stability
  • Flavobacterium / enzymology*
  • Hydrogen-Ion Concentration
  • Kinetics
  • Metalloendopeptidases / chemistry
  • Metalloendopeptidases / isolation & purification*
  • Metalloendopeptidases / metabolism*
  • Molecular Sequence Data
  • Molecular Weight
  • Peptide Fragments / chemistry
  • Protease Inhibitors / pharmacology
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Spectrometry, Mass, Secondary Ion
  • Substrate Specificity
  • Thermodynamics
  • Zinc / analysis

Substances

  • Amino Acids
  • Apoenzymes
  • Cations, Divalent
  • Peptide Fragments
  • Protease Inhibitors
  • Metalloendopeptidases
  • Zinc
  • Calcium