Abstract
The proteinase from the extremely thermophilic Bacillus strain EA.1 exhibits maximum stability at a pH of approx. 6.5. In the presence of calcium ions the half-life at 95 degrees C of the enzyme at this pH was 17 min, and loss of activity followed first-order decay kinetics. The role of metal ions in the activity and stability of the enzyme was studied using the holoenzyme, the metal-depleted apoenzyme, and a zinc-enriched apoenzyme preparation. Zinc and calcium ions were the preferred bivalent cations for the active site and stabilization site(s) respectively. Stabilization by metal ions was not in itself a highly stringent process, but ions other than calcium which stabilized the enzyme generally had a concomitant inhibitory effect on activity. Inhibition and stabilization of the enzyme by cations were concentration-dependent effects and certain ions activated the apoenzyme but not the holoenzyme. Manganese(II) ions conferred some stability and also activated the enzyme, but in the latter case were not as effective as zinc ions. The results are discussed with reference to the ionic radii, co-ordination number and preferred ligand donors of the ions. Mercury(II) ions severely compromised enzyme activity and stability, and the effects of thiol-reactive agents suggest that thiol groups also have a role in enzyme integrity.
MeSH Terms
Apoproteins/metabolism
Bacillus/enzymology
Calcium Chloride/pharmacology
Cations/pharmacology
Cations, Divalent/pharmacology
Enzyme Stability/drug effects
Extracellular Space/enzymology
Heating
Hydrogen-Ion Concentration
Metalloendopeptidases/chemistry,drug effects,metabolism
Metals/pharmacology
Sulfhydryl Compounds/pharmacology
Zinc/pharmacology
Chemicals
Apoproteins
Cations
Cations, Divalent
Metals
Sulfhydryl Compounds
Metalloendopeptidases
microbial metalloproteinases
Zinc
Calcium Chloride
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Coolbear T
Thermophile Research Unit, University of Waikato, Hamilton, New Zealand.
Whittaker J M
Daniel R M
References (16)
16 references, click to expand
-
The conformation of thermolysin.
J Biol Chem. 1974 Dec 25;249(24):8030-44
PMID: 4214815
-
Metallocarboxypeptidases: stability constants and enzymatic characteristics.
J Biol Chem. 1961 Aug;236:2244-9
PMID: 13694603
-
Binding of lanthanide ions to thermolysin.
Biochemistry. 1974 Apr 9;13(8):1719-25
PMID: 4831359
-
The structure of carboxypeptidase A. IX. The x-ray diffraction results in the light of the chemical sequence.
Proc Natl Acad Sci U S A. 1969 Sep;64(1):28-35
PMID: 5263013
-
Interactions of calcium and other metal ions with caldolysin, the thermostable proteinase from Thermus aquaticus strain T351.
Biochem J. 1984 Jul 15;221(2):407-13
PMID: 6383347
-
An interactive computer graphics study of thermolysin-catalyzed peptide cleavage and inhibition by N-carboxymethyl dipeptides.
Biochemistry. 1984 Nov 20;23(24):5730-41
PMID: 6525336
-
Thermal denaturation of streptomyces subtilisin inhibitor, subtilisin BPN', and the inhibitor-subtilisin complex.
Biochemistry. 1981 Oct 13;20(21):6185-90
PMID: 7030385
-
Hypothesis for a neuronal mechanism involved in memory.
Nature. 1972 Jul 7;238(5358):41-3
PMID: 12635271
-
Metallocarboxypeptidases.
J Biol Chem. 1960 Feb;235:390-5
PMID: 13811155
-
Protein engineering of disulfide bonds in subtilisin BPN'.
Biochemistry. 1989 May 30;28(11):4807-15
PMID: 2504281
-
Structure of a calcium-binding carp myogen.
Proc Natl Acad Sci U S A. 1972 Mar;69(3):581-4
PMID: 4501574
-
Metal substitutions and inhibition of thermolysin: spectra of the cobalt enzyme.
J Biol Chem. 1974 Jul 25;249(14):4601-7
PMID: 4843146
-
A high resolution structure of an inhibitor complex of the extracellular nuclease of Staphylococcus aureus. I. Experimental procedures and chain tracing.
J Biol Chem. 1971 Apr 10;246(7):2302-16
PMID: 5555571
-
Binding of N-carboxymethyl dipeptide inhibitors to thermolysin determined by X-ray crystallography: a novel class of transition-state analogues for zinc peptidases.
Biochemistry. 1984 Nov 20;23(24):5724-9
PMID: 6395881
-
Electrochemical photolysis of water at a semiconductor electrode.
Nature. 1972 Jul 7;238(5358):37-8
PMID: 12635268
-
Crystal structure of human carbonic anhydrase C.
Nat New Biol. 1972 Feb 2;235(57):131-7
PMID: 4621826