Matrix metalloproteinase (MMPs) belong to the family of zinc endopeptidases collectively referred to as metzincins. The metzincin superfamily is distinguished by a highly conserved motif containing three histidines that bind to zinc at the catalytic site and a conserved methionine that sits beneath the active site.



Interstitial collagenase, the first MMP family member identified, was initially discovered in experiments designed to explain collagen remodeling in the metamorphosis of a tadpole into a frog1. The MMP family is comprised of more than 20 related zinc-dependent enzymes that share common functional domains. These enzymes have both a descriptive name generally based on a preferred substrate and a MMP numbering system based on order of discovery1.


Structural Characteristics

The basic structure of MMPs is made up of the following homologous domains: 1) Signal peptide which directs MMPs to the secretory or plasma membrane insertion pathway; 2) Prodomain that confers latency to the enzymes by occupying the active site zinc, making the catalytic enzyme inaccessible to substrates; 3) Zinc containing catalytic domain; 4) Hemopexin domain which mediates interactions with substrates and confers specificity of the enzymes; and 5) Hinge region which links the catalytic and the hemopexin domain. The smallest MMP in size, MMP7 or matrilysin, lacks the hemopexin domain, yet displays specificity in substrate degradation. Additional structural domains and substrate specificities have led to the division of MMPs into subgroups.


Two sequence motifs are highly conserved in the protein structure of MMPs. The consensus motif HExGHxxGxxH, found in the catalytic domain of all MMPs, contains 3 histidines that coordinate with the zinc ion (Zn) in the active center. The PRCGxPD motif is located in the C-terminal portion of the prodomain of MMPs; coordination of the cysteine residue (C) of this locus with the zinc atom of the active center confers latency to the proenzyme 2, 3.


Mode of Action

In vivo activity of MMPs is under tight control at several levels. These enzymes are generally expressed in very low amounts and their transcription is tightly regulated either positively or negatively by cytokines and growth factors such as interleukins ( IL-1, IL-4, IL-6), transforming growth factors (EGF, HGF, TGFß), or tumor necrosis factor alpha (TNFa) 4, 5. Some of these regulatory molecules can be proteolytically activated or inactivated by MMPs (feedback effect). Post-transcrpitionally, MMP activity is restricted by the latency conferred by the propeptide located in the N-terminal end of the newly synthesized proenzymes. Activation of MMPs following secretion from cells depends on disruption of the prodomain interaction with the catalytic site, which may occur by conformational changes or proteolytic removal of the prodomain. MMPs that contain furin-like recognition domains in their propeptides (MMP11, MT-MMPs, MMP28) can be activated in the trans-golgi network by members of the subtilisin family of serine proteases. MMP14 plays an integral role in the activation of proMMP2 on the cell surface. Extracellular proteolytic activation of secreted MMPs can be mediated by serine proteases such as plasmin, which implies an interdependence of these two enzyme groups in ECM remodeling . Some active MMPs can activate other proMMPs e.g. MMP3 activation of MMP9 and MMP1. Once activated, MMPs are further regulated by endogenous inhibitors, autodegradation, and selective endocytosis. Endocytosis of MMP2, 9, and 13 through a low density lipoprotein receptor-related protein (LRP) mechanism has been demonstrated 7.



Participation of the MMPs in various aspects of Cancer- MMP-induced release from the cell surface (shedding) of heparin binding epithelial growth factor, insulin-like growth factor, and fibroblast growth factor enhance cell proliferation. On the other hand, release and activation of ECM sequestered TGFß by MMPs can lead to inhibition of cell proliferation.


Inflammatory diseases- Many reports have implicated MMP1, MMP3, and MMP9 involved in rheumatoid and osteoarthritis.


Cardiovascular disease- Numerous studies have demonstrated increased levels of MMPs, especially MMP9, at sites of atherosclerosis and aneurysm formation 6. MMPs have been proposed to represent sensitive markers of inflammation in patients with coronary artery disease.


Lung disease- Elevated levels of MMPs have been implicated in the pathophysiology of various lung diseases, including acute respiratory distress syndrome, asthma, bronchiectasis, and cystic fibrosis. MMPs, EMMPRIN, and TIMPs are produced by many of the resident cells in the lung, hence complicating the analysis of their role in disease 7.


Central Nervous System disease- Following observations of the critical role of MMP9 in animal models resembling multiple sclerosis and Guillain-Barre’s syndrome, MMPs has been implicated in several different types of neurologic diseases .


Shock syndromes- MMP8 and MMP9 are stored in the granules of polymorphonuclear leukocytes. These cells are key effectors in inflammatory and infectious processes. A role for these MMPs in shock is supported by studies in MMP9 deficient mice that were shown to be resistant to endotoxic shock. Dubois et a., 8 proposed that specific MMP9 inhibition constitutes a potential approach for the treatment of septic shock syndromes.



1.     Gross J, Lapiere CM (1962). Collagenolytic activity in amphibian tissues; a tissue culture assay. PNAS., 48:1014-1022.

2.     Nagase H, Woessner F (1999). Matrix metalloproteinases. J Biol Chem., 274(31):21491-21494.

3.     Birkedal-Hansen H. (1995). Proteolytic remodeling of extracellular matrix. Curr Opin Cell Biol., 7:728-735.

4.     Zucker S, Pei D, Cao J, Lopez-Otin C (2003). Membrane type-matrix metalloproteinases (MT-MMP). Cell Surface Proteases., 54:1-74.

5.     Yang Z, Strickland DK, Bornstein P (2001). Extracellular MMP-2 levels  are regulated by the low-density lipoprotein-related scavenger receptor and thrombospondin. J Biol Chem., 276: 8403-8408.

6.     Van den Steen PE, Dubois B, Nelissen I, Rudd PM, Dwek RA, Opdenakker G (2002). Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9). Crit Rev Biochem Mol Biol,. 37:376-536.

7.     Haseneen N, Vaday G, Zucker S, Foda HD (2003). Mechanical stretch induces MMP-2 release and activation in lung endothelium: role of EMMPRIN. Am J Physio Lung Cell Mol Physiol., 165:541-547.

8.     Dubois B, Starckx S, Pagenstecher A, Oord J, Arnold B, Opdenakker G. Gelatinase B (2002). Deficiency protects against endotoxin shock. Eur J Immunol., 32:2163-2171.


If you are unable to find your desired product please contact us for assistance or send an email to info@biosyn.com

Product Name Catalog # Unit Price/Unit 
360 MMP FRET Substrate I
12433-01 1 mg $743 cart inquire
360 MMP FRET Substrate II
12437-01 1 mg $710 cart inquire
360 MMP FRET Substrate III
12442-01 1 mg $710 cart inquire
360 MMP FRET Substrate IV
12444-01 1 mg $710 cart inquire
360 MMP FRET Substrate V
12445-01 1 mg $710 cart inquire
360 MMP FRET Substrate VI
12447-01 1 mg $710 cart inquire
5 - FAM MMP FRET Peptide Fluorescence Standard I
12476-01 1 mg $828 cart inquire
CTT, Gelatinase Inhibitor
CTTHWGFTLC (Disulfide Bridge: 1-10)
12480-01 1 mg $828 cart inquire
MMP Biotinylated Substrate I
12436-01 1 mg $675 cart inquire
MMP Peptide Inhibitor I
12452-01 1 mg $642 cart inquire
STT Gelatinase Inhibitor modification, negative co
12479-01 1 mg $710 cart inquire

Biosynthesis Inc.