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{PDOC00472}
{PS00546; CYSTEINE_SWITCH}
{BEGIN}
*****************************
* Matrixins cysteine switch *
*****************************
Mammalian extracellular matrix metalloproteinases (EC 3.4.24.-), also known as
matrixins [1] (see <PDOC00129>), are zinc-dependent enzymes. They are secreted
by cells in an inactive form (zymogen) that differs from the mature enzyme by
the presence of an N-terminal propeptide. A highly conserved octapeptide is
found two residues downstream of the C-terminal end of the propeptide. This
region has been shown to be involved in autoinhibition of matrixins [2,3];
a cysteine within the octapeptide chelates the active site zinc ion, thus
inhibiting the enzyme. This region has been called the 'cysteine switch' or
'autoinhibitor region'.
A cysteine switch has been found in the following zinc proteases:
- MMP-1 (EC 3.4.24.7) (interstitial collagenase).
- MMP-2 (EC 3.4.24.24) (72 Kd gelatinase).
- MMP-3 (EC 3.4.24.17) (stromelysin-1).
- MMP-7 (EC 3.4.24.23) (matrilysin).
- MMP-8 (EC 3.4.24.34) (neutrophil collagenase).
- MMP-9 (EC 3.4.24.35) (92 Kd gelatinase).
- MMP-10 (EC 3.4.24.22) (stromelysin-2).
- MMP-11 (EC 3.4.24.-) (stromelysin-3).
- MMP-12 (EC 3.4.24.65) (macrophage metalloelastase).
- MMP-13 (EC 3.4.24.-) (collagenase 3).
- MMP-14 (EC 3.4.24.-) (membrane-type matrix metalliproteinase 1).
- MMP-15 (EC 3.4.24.-) (membrane-type matrix metalliproteinase 2).
- MMP-16 (EC 3.4.24.-) (membrane-type matrix metalliproteinase 3).
- Sea urchin hatching enzyme (EC 3.4.24.12) (envelysin) [4].
- Chlamydomonas reinhardtii gamete lytic enzyme (GLE) [5].
-Consensus pattern: P-R-C-[GN]-x-P-[DR]-[LIVSAPKQ]
[C chelates the zinc ion]
-Sequences known to belong to this class detected by the pattern: ALL, except
for cat MMP-7 and mouse MMP-11.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: November 1997 / Pattern and text revised.
[ 1] Woessner J.F. Jr.
"Matrix metalloproteinases and their inhibitors in connective tissue
remodeling."
FASEB J. 5:2145-2154(1991).
PubMed=1850705
[ 2] Sanchez-Lopez R., Nicholson R., Gesnel M.C., Matrisian L.M.,
Breathnach R.
J. Biol. Chem. 263:11892-11899(1988).
[ 3] Park A.J., Matrisian L.M., Kells A.F., Pearson R., Yuan Z.Y., Navre M.
"Mutational analysis of the transin (rat stromelysin) autoinhibitor
region demonstrates a role for residues surrounding the 'cysteine
switch'."
J. Biol. Chem. 266:1584-1590(1991).
PubMed=1988438
[ 4] Lepage T., Gache C.
"Early expression of a collagenase-like hatching enzyme gene in the
sea urchin embryo."
EMBO J. 9:3003-3012(1990).
PubMed=2167841
[ 5] Kinoshita T., Fukuzawa H., Shimada T., Saito T., Matsuda Y.
"Primary structure and expression of a gamete lytic enzyme in
Chlamydomonas reinhardtii: similarity of functional domains to matrix
metalloproteases."
Proc. Natl. Acad. Sci. U.S.A. 89:4693-4697(1992).
PubMed=1584806
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