How do TIMPs inhibit MMPs?

TIMps are able to inhibit MMPs through forming noncovalent complexes with MMPs. TIMPs are crucial for sustaining balance between formation and matrix destruction. TIMPS are unique inhibitors that bind MMPs with a 1:1 stoichiometry. There have been four TIMPs (TIMP-1, TIMP-2, TIMP-3, TIMP-4) that have been identified in vertebrates. TIMP-1 and TIMP-2 have been shown to inhibit tumor-induced angiogenesis in several bioassays. TIMP-3 is only found in the ECM; it is regulated in a cell-cycle dependent manner and inhibits neovascularization. TIMP-3 functions in a tissue specific manner in the matrix hemostasis. 

All MMPs are inhibited by TIMPs once they become activated, and MMP-2 and MMP-9 can form complexes with TIMPs when they are in their unactivated form. The expression of TIMPs is regulated during tissue remodeling and development; changes of TIMP levels directly affect the level of MMP activity. MMPs are typically inhibited by the N-terminal domains of TIMPs.