The C-terminal domains of TACE weaken the inhibitory action of N-TIMP-3 |
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Authors: | Lee Meng-Huee Verma Vandana Maskos Klaus Becherer J David Knäuper Vera Dodds Philippa Amour Augustin Murphy Gillian |
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Institution: | Department of Pathology, University of Tennessee Health Science Center, Memphis, TN 38163, USA. aslominski@utmem.edu |
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Abstract: | Tumor necrosis factor-alpha 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. |
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Keywords: | N-TIMP-3 TACE-cat TACE-long Binding affinity Association rate constants |
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