PS00546

Matrixins cysteine switch

PROSITE patterns entry
Member databasePROSITE patterns
PROSITE patterns typeconserved site
Short nameCYSTEINE_SWITCH

Description

Mammalian extracellular matrix metalloproteinases (EC 3.4.24.-), also known as matrixins
[2]
, 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
[1]
; 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)
[3]
. - Chlamydomonas reinhardtii gamete lytic enzyme (GLE)
[4]
.

References

1.Mutational analysis of the transin (rat stromelysin) autoinhibitor region demonstrates a role for residues surrounding the "cysteine switch". Park AJ, Matrisian LM, Kells AF, Pearson R, Yuan ZY, Navre M. J. Biol. Chem. 266, 1584-90, (1991). View articlePMID: 1988438

2.Matrix metalloproteinases and their inhibitors in connective tissue remodeling. Woessner JF Jr. FASEB J. 5, 2145-54, (1991). View articlePMID: 1850705

3.Early expression of a collagenase-like hatching enzyme gene in the sea urchin embryo. Lepage T, Gache C. EMBO J. 9, 3003-12, (1990). View articlePMID: 2167841

4.Primary structure and expression of a gamete lytic enzyme in Chlamydomonas reinhardtii: similarity of functional domains to matrix metalloproteases. Kinoshita T, Fukuzawa H, Shimada T, Saito T, Matsuda Y. Proc. Natl. Acad. Sci. U.S.A. 89, 4693-7, (1992). View articlePMID: 1584806

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