title: Effects of heparin and cholesterol sulfate on the activity and stability of human matrix metalloproteinase 7.
abstract: Sulfated glycosaminoglycans and sulfated lipids are involved in the biological functions of human matrix metalloproteinase 7 (MMP-7). In this study, the effects of heparin and cholesterol sulfate (CS) on the activity and stability of MMP-7 in the hydrolysis of a synthetic substrate, (7-methoxycoumarin-4-yl)acetyl-l-Pro-l-Leu-Gly-l-Leu-[N(3)-(2,4-dinitrophenyl)-l-2,3-diaminopropionyl]-l-Ala-l-Arg-NH2, were examined. Heparin increased activity by decreasing Km, and the Km values for 0 and 50 μM heparin were 57 ± 8 and 19 ± 5 μM, respectively. CS decreased activity in a non-competitive inhibitory manner with a Ki value of 11 ± 3 μM. In thermal incubation at 50-70 °C, heparin increased relative activity (the ratio of kcat/Km of MMP-7 with incubation to that without it), while CS decreased relative activity. These results indicate that heparin increases the activity and stability of MMP-7, while CS decreases them.
authors.affiliation: a Division of Food Science and Biotechnology , Graduate School of Agriculture, Kyoto University , Kyoto , Japan.
authors.forename: Vimbai
authors.initials: V
authors.lastname: Samukange
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yasukawa
authors.forename: Kuniyo
authors.initials: K
authors.lastname: Inouye
mesh_terms: D002460:Cell Line; D002788:Cholesterol Esters / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology*; D004795:Enzyme Stability / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000737:chemistry* / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*
chemical_list: D002788:Cholesterol Esters; D020536:Enzyme Activators; D061965:Matrix Metalloproteinase Inhibitors; D006493:Heparin; D020783:Matrix Metalloproteinase 7; C007045:cholesteryl sulfate
keywords: MMP-7; cholesterol sulfate; heparin; matrix metalloproteinase