The C-terminal domains of TACE weaken the inhibitory action of N-TIMP-3

Meng Huee Lee*, Vandana Verma, Klaus Maskos, J. David Becherer, Vera Knäuper, Philippa Dodds, Augustin Amour, Gillian Murphy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)


Tumor necrosis factor-α converting enzyme (TACE) is an ADAM (a disintegrin and metalloproteinases) that comprises an active catalytic domain and several C-terminal domains. We compare the binding affinity and association rate constants of the N-terminal domain form of wild-type tissue inhibitor of metalloproteinase (TIMP-3; N-TIMP-3) and its mutants against full-length recombinant TACE and the truncated form of its catalytic domain. We show that the C-terminal domains of TACE substantially weaken the inhibitory action of N-TIMP-3. Further probing with hydroxamate inhibitors indicates that both forms of TACE have similar active site configurations. Our findings highlight the potential role of the C-terminal domains of ADAM proteinases in influencing TIMP interactions.

Original languageEnglish
Pages (from-to)102-106
Number of pages5
JournalFEBS Letters
Issue number1-3
Publication statusPublished - 5 Jun 2002
Externally publishedYes


  • Association rate constants
  • Binding affinity
  • N-TIMP-3
  • TACE-cat
  • TACE-long

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