Overview for MACiE Entry M0176

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General Information

EC Number: (A member of the Hydrolases, Acting on peptide bonds (peptidases), Metalloendopeptidases)

Enzyme Name: thermolysin

Biological Species: Bacillus thermoproteolyticus (Bacteria)

Catalytic Chain UniprotKB Accession Codes:

Representative PDB Code: 1kei - THERMOLYSIN (SUBSTRATE-FREE) (Resolution = 1.60 Å).

Catalytic CATH Codes:

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Overall Reaction:

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C-terminus of a protein
N-terminus of a protein

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Stepwise Description of the Reaction

Step 1His231 deprotonates water, which attacks the peptide bond in a nucleophilic addition, resulting in the coordination of the oxyanion to the zinc cofactor.
Step 2The oxyanion initiates an elimination that cleaves the peptide bond. The N-terminal product deprotonates His231.
Step 3The N-terminal product then deprotonates the C-terminal product to form the kinetically favoured products.

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Catalytic Residues Involved

Type Number Chain Location of Function
Glu 143 A Side Chain
Tyr 157 A Side Chain
Asp 226 A Side Chain
His 231 A Side Chain

Metal Cofactors for M0176

Type Het group Number Chain
zinc ZN 405 A Overview


  1. W. L. Mock et al. (1996), Biochemistry, 35, 7369-7377. Arazoformyl dipeptide substrates for thermolysin. Confirmation of a reverse protonation catalytic mechanism.
    Medline: 8652513
  2. C. Marie-Claire et al. (1998), FEBS Letters, 438, 215-219. Differences in transition state stabilization between thermolysin (EC and neprilysin (EC
    Medline: 9827548
  3. D. H. Juers et al. (2005), Biochemistry, 44, 16524-16528. Structural analysis of silanediols as transition-state-analogue inhibitors of the benchmark metalloprotease thermolysin.
    Medline: 16342943

Homologue information for M0176 (1kei)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)

Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
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Link to EzCatDB

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metalloendopeptidase activity (molecular function)
extracellular region (cellular component)
proteolysis (biological process)
peptidase activity (molecular function)
metallopeptidase activity (molecular function)
zinc ion binding (molecular function)
hydrolase activity (molecular function)
metal ion binding (molecular function)