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Key residues in the prodomain of TACE determining its inhibition of the catalytic domain
Author(s) -
Milla Marcos E,
Gonzales Patricia E
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a647-c
Subject(s) - furin , zymogen , chemistry , enzyme , residue (chemistry) , microbiology and biotechnology , catalysis , mutant , biochemistry , biology , gene
The TNFα converting enzyme (TACE) mediates the regulated shedding of a host of cell surface proteins. Regulation of TACE shedding is ultimately mediated by its activation from a zymogen state via proteolytic removal of its inhibitory prodomain by furin. Here we show that potent inhibition of the catalytic domain of TACE by its prodomain is determined by specific residues located in two distinct and unique segments of this 214‐residue domain. By analyzing the functional protperties of TACE/ADAM10 prodomain chimeras and selected point mutants, we have identified a small set of residues that are critical for TACE prodomain binding and inhibition of the catalytic domain of this enzyme.