MMP

Full name: Matrix metalloproteinase

Size:1,2 Multidomain proteins with globular catalytic domains that are ~130–260 residues in length

Family:1-3 Belongs to the metzincin superfamily of MMPs; 23 structurally and functionally related members can be divided into six groups: collagenases (MMP-1, MMP-8, MMP-13, and MMP-18), gelatinases (MMP-2 and MMP-9), stromelysins (MMP-3, MMP-10, and MMP-11), matrilysins (MMP-7 and MMP-26), membrane-type MMPs (MMP-14, MMP-15, MMP-16, MMP-17, MMP-24, and MMP-25), and other non-classified MMPs

Major cellular sources:3 Fibroblasts, neutrophils, monocytes, and macrophages

Disease states associated with:2 Arthritis, chronic obstructive pulmonary disease, sepsis, and cancer

Major physiologic functions:

  • MMPs are proteolytic enzymes involved in physiological processes, including angiogenesis, wound healing, embryonic development, and regulation of inflammation.2

  • MMP activity is almost undetectable under normal physiological conditions but can be observed during processes such as angiogenesis, wound healing, bone formation, and mammary gland involution.1

  • MMP activity is strongly regulated by natural MMP inhibitors called TIMPs. High TIMP levels lead to ECM accumulation due to inhibition of the degradation process, whereas low TIMP activity leads to elevated proteolysis. This dysregulation between MMPs and TIMPs results in increased MMP activity and diseases such as arthritis, COPD, sepsis or cancer.2

  • MMPs are zinc- and calcium-dependent endopeptidases that decompose proteins, including themselves through autoproteolysis. This catalytic activity is brought about through the mechanism of a “cysteine switch” that enables a water molecule to coordinate with catalytic zinc.2

  • Members of the MMP family collectively are capable of degrading all structural components of the ECM.1 Thus, MMPs are important regulators of cellular activities that are involved in several physiological and pathological processes, including reproduction, embryogenesis, angiogenesis, and tissue remodeling.1,3

  • Furthermore, MMPs are involved in the release and activation of bound signaling molecules, including chemokines, cytokines, and growth factors, thus contributing to different aspects of immunity.1

ECM: extracellular matrix; TIMP: tissue inhibitor of metalloproteinase.

References:

  • 1.

    Vandenbroucke RE, Libert C. Nat Rev Drug Discov. 2014;13:904-927.

  • 2.

    Fischer T, Riedl R. Molecules. 2019;24:2265.

  • 3.

    Jabłońska-Trypuć A, Matejczyk M, Rosochacki S. J Enzyme Inhib Med Chem. 2016;31(suppl 1):177-183.