The 84-kDa form of human matrix metalloproteinase-9 degrades substance P and gelatin.
Matrix metalloproteinase-9 (MMP-9) is secreted from cells and, once activated, is thought to degrade collagen in the extracellular matrix. Because collagen is not readily localized where neurons have been shown to produce MMP-9 in the human brain, the ability of this enzyme to degrade bioactive peptides was investigated with representative tachykinin peptides [substance P (SP), neurokinin A, neurokinin B, and kassinin]. Latent MMP-9 (94 kDa) was purified from the human cell line HL-60 and converted to an intermediary active form (84 kDa) with p-aminophenylmercuric acetate. This active form of MMP-9 degraded SP with a kcat/Km of 170 mM-1 min-1, which is 30-fold greater than the previously reported value for a representative collagen-derived peptide. The major digestion products were identified as SP and SP, which were derived from cleavage of the Gln6-Phe7 bond. Minor products were also generated from cleavage of the Gly9-Leu10 bond. The other representative tachykinin peptides were cleaved at rates > 10-fold slower than that of SP. The 84-kDa peptidase was also active as a gelatinase. Longer treatment of MMP-9 with p-aminophenylmercuric acetate caused the conversion of the 84-kDa enzyme to the established 68-kDa active form; however, the rate of SP degradation did not increase. Because MMP-9 is produced by neurons of the CNS, these results suggest a possible regulatory role for the enzyme in interacellular communication by altering the availability of bioactive peptides.
Backstrom
J R
JR
Department of Biochemistry and Molecular Biology, School of Medicine, University of Southern California, Los Angeles.
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D000595:Amino Acid Sequence; D002460:Cell Line; D017364:Collagenases / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D005780:Gelatin / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D020780:Matrix Metalloproteinase 9; D008969:Molecular Sequence Data; D008970:Molecular Weight; D013373:Substance P / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
D013373:Substance P; D005780:Gelatin; D017364:Collagenases; D020780:Matrix Metalloproteinase 9