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

FEBS Letters

Maskos, Klaus³  Becherer, J.David⁴  Amour, Augustin²  Murphy, Gillian¹  Dodds, Philippa¹  Lee, Meng-Huee¹  Knäuper, Vera¹  Verma, Vandana¹ 

[1] School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK;Glaxo Smith Kline, Stevenage, Herts SG1 2NY, UK;Max-Planck Institut für Biochemie, D-82152 Martinsried, Germany;Glaxo Smith Kline Research and Development Inc., 5 Moore Drive, Research Triangle Park, NC 27709, USA

关键词: N-TIMP-3;    TACE-cat;    TACE-long;    Binding affinity;    Association rate constants;    TIMP-3;    tissue inhibitor of metalloproteinases-3;    TNF-α;    tumor necrosis factor-α;    TACE;    tumor necrosis factor-α converting enzyme;    ADAM-TS;    ADAM proteinase with thrombospondin domains;    Mca;    (7-methoxycoumarin-4-yl)acetyl;    Dnp;    2;    4-dinitrophenyl;   

DOI  :  10.1016/S0014-5793(02)02776-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Tumor necrosis factor-α converting enzyme (TACE) is an ADAM ( isintegrin nd etalloproteinases) 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.

【 授权许可】

Unknown