Matrix metalloproteinase-2 is an interstitial collagenase. Inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3/4- and 1/4-length fragments.
The 72-kDa gelatinase/type IV collagenase (MMP-2) is a member of the matrix metalloproteinase (MMP) family of enzymes. This enzyme is known to cleave type IV collagen as well as degrade denatured collagens. However, native interstitial collagens are reportedly resistant to MMP-2 and are thought to be susceptible only to the interstitial collagenases MMP-1 and MMP-8. In this study we report that both human and chicken MMP-2, free of tissue inhibitors of metalloproteinases (TIMPs) are capable of cleaving soluble, triple helical type I collagen generating the 3/4- and 1/4-length collagen fragments characteristic of vertebrate interstitial collagenases. MMP-2 cleaves at the same Gly-Ile/Leu bond in the collagen alpha chains as interstitial collagenases with kcat and Km values similar to that of MMP-1. MMP-2 also is capable of degrading reconstituted type I collagen fibrils. The closely related 92-kDa gelatinase/type IV collagenase (MMP-9) is unable to cleave soluble or fibrillar collagen under identical conditions indicating that the specific collagenolytic activity of MMP-2 is not a general property of gelatinases. That MMP-2, a potent gelatinase, also can cleave fibrillar collagen provides an alternative to the proposal that two enzymes, an interstitial collagenase and a gelatinase, are required for the complete dissolution of stromal collagen during cellular invasion.
Aimes
R T
RT
Department of Biochemistry and Cell Biology, State University of New York, Stony Brook 11794.
Quigley
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002645:Chickens; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D018093:Gelatinases / Q000302:isolation & purification / Q000378:metabolism*; D006023:Glycoproteins / Q000302:isolation & purification; D006801:Humans; D007700:Kinetics; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8; D008666:Metalloendopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D051381:Rats; D012867:Skin; D013379:Substrate Specificity; D013710:Tendons; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D010446:Peptide Fragments; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8; D020781:Matrix Metalloproteinase 1