Tissue inhibitors of metalloproteinases: evolution, structure and function
- PMID: 10708863
- DOI: 10.1016/s0167-4838(99)00279-4
Tissue inhibitors of metalloproteinases: evolution, structure and function
Abstract
The matrix metalloproteinases (MMPs) play a key role in the normal physiology of connective tissue during development, morphogenesis and wound healing, but their unregulated activity has been implicated in numerous disease processes including arthritis, tumor cell metastasis and atherosclerosis. An important mechanism for the regulation of the activity of MMPs is via binding to a family of homologous proteins referred to as the tissue inhibitors of metalloproteinases (TIMP-1 to TIMP-4). The two-domain TIMPs are of relatively small size, yet have been found to exhibit several biochemical and physiological/biological functions, including inhibition of active MMPs, proMMP activation, cell growth promotion, matrix binding, inhibition of angiogenesis and the induction of apoptosis. Mutations in TIMP-3 are the cause of Sorsby's fundus dystrophy in humans, a disease that results in early onset macular degeneration. This review highlights the evolution of TIMPs, the recently elucidated high-resolution structures of TIMPs and their complexes with metalloproteinases, and the results of mutational and other studies of structure-function relationships that have enhanced our understanding of the mechanism and specificity of the inhibition of MMPs by TIMPs. Several intriguing questions, such as the basis of the multiple biological functions of TIMPs, the kinetics of TIMP-MMP interactions and the differences in binding in some TIMP-metalloproteinase pairs are discussed which, though not fully resolved, serve to illustrate the kind of issues that are important for a full understanding of the interactions between families of molecules.
Similar articles
-
Sequence motifs of tissue inhibitor of metalloproteinases 2 (TIMP-2) determining progelatinase A (proMMP-2) binding and activation by membrane-type metalloproteinase 1 (MT1-MMP).Biochem J. 2003 Jun 15;372(Pt 3):799-809. doi: 10.1042/BJ20021573. Biochem J. 2003. PMID: 12630911 Free PMC article.
-
Tissue inhibitor of metalloproteinases-4 inhibits but does not support the activation of gelatinase A via efficient inhibition of membrane type 1-matrix metalloproteinase.Cancer Res. 2001 May 1;61(9):3610-8. Cancer Res. 2001. PMID: 11325829
-
E. coli expression of TIMP-4 and comparative kinetic studies with TIMP-1 and TIMP-2: insights into the interactions of TIMPs and matrix metalloproteinase 2 (gelatinase A).Biochemistry. 2002 Dec 17;41(50):15025-35. doi: 10.1021/bi026454l. Biochemistry. 2002. PMID: 12475252
-
Insights into MMP-TIMP interactions.Ann N Y Acad Sci. 1999 Jun 30;878:73-91. doi: 10.1111/j.1749-6632.1999.tb07675.x. Ann N Y Acad Sci. 1999. PMID: 10415721 Review.
-
Matrix metalloproteinases and their inhibitors.Anticancer Res. 1999 Mar-Apr;19(2C):1589-92. Anticancer Res. 1999. PMID: 10365151 Review.
Cited by
-
Relationship between CCL25/CCR9 Levels in Follicular Fluid and High Ovarian Response in Patients with Polycystic Ovary Syndrome.Int J Endocrinol. 2024 Oct 3;2024:2449037. doi: 10.1155/2024/2449037. eCollection 2024. Int J Endocrinol. 2024. PMID: 39411316 Free PMC article.
-
Genetics and pathogenesis of scoliosis.N Am Spine Soc J. 2024 Sep 6;20:100556. doi: 10.1016/j.xnsj.2024.100556. eCollection 2024 Dec. N Am Spine Soc J. 2024. PMID: 39399722 Free PMC article.
-
Navigating the Landscape of Coronary Microvascular Research: Trends, Triumphs, and Challenges Ahead.Rev Cardiovasc Med. 2024 Aug 16;25(8):288. doi: 10.31083/j.rcm2508288. eCollection 2024 Aug. Rev Cardiovasc Med. 2024. PMID: 39228508 Free PMC article. Review.
-
Emerging Therapeutic Targets for Acute Coronary Syndromes: Novel Advancements and Future Directions.Biomedicines. 2024 Jul 26;12(8):1670. doi: 10.3390/biomedicines12081670. Biomedicines. 2024. PMID: 39200135 Free PMC article. Review.
-
Microparticle Mediated Delivery of Apelin Improves Heart Function in Post Myocardial Infarction Mice.Circ Res. 2024 Sep 13;135(7):777-798. doi: 10.1161/CIRCRESAHA.124.324608. Epub 2024 Aug 15. Circ Res. 2024. PMID: 39145385
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous