The isolated N-terminal domains of TIMP-1 and TIMP-3 are insufficient for ADAM10 inhibition

The Biochemical Journal
Magdalini RaptiGillian Murphy

Abstract

ADAM (a disintegrin and metalloproteinase) 10 is a key member of the ADAM family of disintegrin and metalloproteinases which process membrane-associated proteins to soluble forms in a process known as 'shedding'. Among the major targets of ADAM10 are Notch, EphrinA2 and CD44. In many cell-based studies of shedding, the activity of ADAM10 appears to overlap with that of ADAM17, which has a similar active-site topology relative to the other proteolytically active ADAMs. The tissue inhibitors of metalloproteinases, TIMPs, have proved useful in the study of ADAM function, since TIMP-1 inhibits ADAM10, but not ADAM17; however, both enzymes are inhibited by TIMP-3. In the present study, we show that, in comparison with ADAM17 and the MMPs (matrix metalloproteinases), the N-terminal domains of TIMPs alone are insufficient for the inhibition of ADAM10. This knowledge could form the basis for the design of directed inhibitors against different metalloproteinases.

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Citations

May 24, 2008·Circulation Research·Bharathy Ponnuchamy, Raouf A Khalil
Sep 13, 2011·Clinical Proteomics·Michael J DuffyPatricia M McGowan
Aug 1, 2009·Matrix Biology : Journal of the International Society for Matrix Biology·Linda TroebergHideaki Nagase
Aug 25, 2015·Neurobiology of Disease·Katie Z ChapmanZaal Kokaia
Sep 16, 2010·The FEBS Journal·Tina Manon-JensenJohn R Couchman
Nov 3, 2015·Journal of Molecular and Cellular Cardiology·Pu ZhangZamaneh Kassiri
Nov 15, 2011·Biomaterials·David E RobinsonJason D Whittle
Aug 31, 2014·Immunology Letters·Sabrina LisiMargherita Sisto
Sep 19, 2019·Cancer Metastasis Reviews·Celina EckfeldAchim Krüger
Oct 15, 2019·Frontiers in Aging Neuroscience·Laura García-GonzálezSantiago Rivera
Aug 16, 2021·The Journal of Biological Chemistry·Benjamin SchoepsAchim Krüger

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