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Activation of ADAM 12 protease by copper
Author(s) -
Loechel Frosty,
Wewer Ulla M.
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02873-3
Subject(s) - disintegrin , cysteine , furin , metalloproteinase , protein precursor , chemistry , mutant , copper , proteases , protease , biochemistry , cleavage (geology) , cysteine protease , matrix metalloproteinase , enzyme , biology , gene , paleontology , organic chemistry , fracture (geology)
Conversion of latent proteases to the active form occurs by various mechanisms characteristic for different protease families. Here we report that the disintegrin metalloprotease ADAM 12‐S is activated by Cu(II). Copper activation is distinct from the cysteine switch component of latency: elimination of the ADAM 12 cysteine switch by a point mutation in the propeptide had no effect on copper activation, whereas mutation of an unpaired cysteine residue in the catalytic domain resulted in a mutant form of ADAM 12‐S that was insensitive to copper. This suggests a multi‐step activation mechanism for ADAM 12 involving both furin cleavage and copper binding.