Structure of human pro-matrix metalloproteinase-2: activation mechanism revealed.
Matrix metalloproteinases (MMPs) catalyze extracellular matrix degradation. Control of their activity is a promising target for therapy of diseases characterized by abnormal connective tissue turnover. MMPs are expressed as latent proenzymes that are activated by proteolytic cleavage that triggers a conformational change in the propeptide (cysteine switch). The structure of proMMP-2 reveals how the propeptide shields the catalytic cleft and that the cysteine switch may operate through cleavage of loops essential for propeptide stability.
Morgunova
E
E
Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Tuuttila
A
A
Bergmann
U
U
Isupov
M
M
Lindqvist
Y
Y
Schneider
G
G
Tryggvason
K
K
D000595:Amino Acid Sequence; D020134:Catalytic Domain; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000737:chemistry* / Q000378:metabolism; D005353:Fibronectins / Q000737:chemistry; D018093:Gelatinases / Q000737:chemistry* / Q000378:metabolism; D006466:Hemopexin / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary
D004792:Enzyme Precursors; D005353:Fibronectins; D006466:Hemopexin; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2