This document summarizes matrix metalloproteinases (MMPs), a family of enzymes that degrade the extracellular matrix and are involved in tissue remodeling. It groups MMPs into collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs, and others. For each group, it lists the MMP names and their protein substrates. It also describes two pathways for activating MMPs at the cell surface, and discusses transcriptional regulation, activation of precursors, substrate specificity, inhibitors like TIMPs and α2-macroglobulins, and classes of pharmacological MMP inhibitors.

1. PUNIT
PG STUDENT

13. Group MMPs Nomenclature Group substrate
Collagenases MMP-1 Collagenase 1,
fibroblast collagenase
Types I, II, III, VII, X, XI
collagens, gelatin, entactin,
aggrecan, tenascin, perlecan,
vitronectin, α2Ma
MMP-8 Collagenase 2,
neutrophil collagenase
Types I, II, III, VII, X collagen,
gelatin, aggrecan, entactin,
tenascin, tissue factor pathway
inhibitor, α2Ma
MMP-13 Collagenase 3 Type I, II, III, IV, VI, VII, X, IX,
XIV collagen, gelatin, fibronectin,
entactin, aggrecan, tenascin

14. Group MMPs Nomenclature Group substrate
Gelatinases MMP-2 Gelatinase A Types I, III, IV, V, VII, X,
XI collagens, gelatin,
elastin, fibronectin,
laminin, aggrecan,
vitronectin
MMP-9 Gelatinase B Types I, IV, V, VII, X, XI,
XIV, XVII,
gelatin, elastin, fibronectin,
laminin,
aggrecan, vitronectin,
decorin,
plasminogen, proTNF-α

15. Group MMPs Nomenclature Group substrate
Stromelysins MMP-3 Stromelysin 1 Types III, IV, V, IX, X, XI
collagens,
elastin, proteoglycans, laminin,
fibronectin, gelatin, fibrin/
fibrinogen,
.aggrecan, vitronectin, perlecan,
decorin, proIL-1bc,
plasminogen, Ecadherin,
α2Ma, proTNF-α
MMP-10 Stromelysin 2 Types III, IV, V, IX, X, XI,
proteoglycans,
laminin, fibronectin, gelatin,
aggrecan,
elastin, fibrin/ fibrinogen,
vitronectin
MMP-11 Stromelysin 3 Unknown

16. Group MMPs Nomenclature Group substrate
Matrilysins MMP-7 Matrilysin 1, PUMP-1 Elastin, proteoglycans,
laminin,
fibronectin, gelatin, types I, III,
IV, V, IX,
X, XI collagens,
fibrin/fibrinogen,
tenascin, vitronectin, pro α-
defensin,
decorin, E- cadherin,
plasminogen,
proTNF-α .
MMP-26 Matrilysin 2 Fibronectin, fibrinogen,
gelatin, type IV
collagen,,laminin-1.

17. Group MMPs Nomenclature Group substrate
Membrane type
MMPs
MMP-14 MT1-MMP Types I, II, III collagens, gelatin,
fibronectin, tenascin, perlecan,
nidogen, vitronectin,factor XII,
fibrin, proTNFα,
laminin, cartilage proteoglycan core
protein, α2Ma, .
.
MMP-15 MT2-MMP Laminin, fibronectin, tenascin,
nidogen,
entactin, gelatin, aggrecan,
vitronectin,
proTNF-ab, transglutaminase
MMP-16 MT3-MMP Gelatin, type III collagen, perlecan,
fibronectin, vitronectin, aggrecan,
transglutaminase.
MMP-17 MT4-MMP Gelatin, fibrin/fibrinogen, α2Ma,
proTNF-α.
MMP-24 MT5-MMP Proteoglycan, type I collagen,
fibronectin,
laminin.
MMP-25 MT6-MMP Gelatin, type IV collagen, fibronectin

18. Group MMPs Nomenclature Group substrate
OTHERS
MMPs
MMP-12 Macrophage elastase MMP-12 Types I, IV collagen,
(Metallo elastase) aggrecan, decorin,
gelatin,
elastin, fibronectin, fibrin/fibrinogen,
laminin, proteoglycan, vitronectin,
plasminogen, α2Ma,
MMP-18 Type I collagen
MMP-19 (No trivial name) Type I and IV collagens, fibronectin,
gelatin, tenascin, casein, laminin,
entactin, aggrecan.
MMP-20 Enamelysin Amelogenin, casein, gelatin, lysin)
(Ename fibronectin, type IV, XVIII
collagens,
laminin, tenascin C, aggrecan
MMP-27 Type II collagen, gelatin, fibronectin
MMP-28 Epilysin Casein

19. Collagenases

23. Gelatinases

26. Stromelysins

30. Matrilysins

33. Membrane type MMP

37. Two pathways are now well characterized that lead to the activation of metalloproteinases at or
near the cell surface. One pathway (a) involves the generation of the serine proteinase plasmin
from plasminogen; this is brought about by the binding of plasminogen activator (PA) to its
membrane receptor (uPAR). Plasmin can activate most prometalloproteinases. The second
pathway (b) involves membrane-bound metalloproteinases that act on certain
prometdoproteinases (in the case of gelatinase A it is a progelatinase AITIMP-2 complex that
becomes bound. There is likely to be overlap and interaction between the two pathways, specific
to each situation. Activation may also take place away from the cell surface if appropriate
proteolytic activity is available for modifying the proenzyme forms of metalloproteinases.

43. Biological action of MMPs

47. REGULATION OF MMPS

48. Transcriptional regulation

49. Activation of precursors

51. Substrate Specificity

52. Inhibitors of MMPs

53. α 2-macroglobulins

54. Tissue inhibitors of metalloproteinases (TIMPs)

59. Agent Class MMP Inhibition
Batimastat Peptido-mimetic MMP-1, 2, 3, 7, 9
Marimastat Peptido-mimetic MMP-1, 2, 3, 7, 9, 12
AG3340
(prinomastat)
Nonpeptido-mimetic MMP-2, 3, 9, 13, 14
BAY 12-9566 Nonpeptido-mimetic MMP-2, 3, 9
MMI270 Nonpeptido-mimetic MMP-1, 2, 3, 9, 13, 14
COL-3 (metastat) Tetracycline derivative MMP-2, 9
BMS-275291 Nonpeptido-mimetic MMP-2, 9
CP-471,358 Nonpeptido-mimetic MMP-2, 3, 8, 9, 12,