Effects of detergents on catalytic activity of human endometase/matrilysin 2, a putative cancer biomarker.
Matrix metalloproteinases (MMPs) are a family of hydrolytic enzymes that play significant roles in development, morphogenesis, inflammation, and cancer invasion. Endometase (matrilysin 2 or MMP-26) is a putative early biomarker for human carcinomas. The effects of the ionic and nonionic detergents on catalytic activity of endometase were investigated. The hydrolytic activity of endometase was detergent concentration dependent, exhibiting a bell-shaped curve with its maximum activity near the critical micelle concentration (CMC) of nonionic detergents tested. The effect of Brij-35 on human gelatinase B (MMP-9), matrilysin (MMP-7), and membrane-type 1 MMP (MT1-MMP) was further explored. Their maximum catalysis was observed near the CMC of Brij-35 ( approximately 90muM). Their IC(50) values were above the CMC. The inhibition mechanism of MMP-7, MMP-9, and MT1-MMP by Brij-35 was a mixed type as determined by Dixon's plot; however, the inhibition mechanism of endometase was noncompetitive with a K(i) value of 240muM. The catalytic activities of MMPs are influenced by detergents. Monomer of detergents may activate and stabilize MMPs to enhance catalysis, but micelle of detergents may sequester enzyme and block the substrate binding site to impede catalysis. Under physiological conditions, a lipid or membrane microenvironment may regulate enzymatic activity.
Park
Hyun I
HI
Department of Chemistry and Biochemistry and Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA.
Lee
Seakwoo
S
Ullah
Asad
A
Cao
Qiang
Q
Sang
Qing-Xiang Amy
QX
D014408:Biomarkers, Tumor / Q000378:metabolism; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003902:Detergents / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism*; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism
D014408:Biomarkers, Tumor; D003902:Detergents; D008823:Micelles; D011092:Polyethylene Glycols; C410599:MMP26 protein, human; D053505:Matrix Metalloproteinases, Secreted; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9; D053511:Matrix Metalloproteinase 14; C515901:Brij 35