Activation of snake venom metalloproteinases by a cysteine switch‐like mechanism

Grams, Frank; Huber, Robert; Kress, Lawrence F.; Moröder, Luis; Bode, Wolfram

doi:10.1016/0014-5793(93)80443-x

Cited by 114 publications

(60 citation statements)

References 30 publications

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“…Moreover, the active form of these metalloproteinases has a shortage of prodomain from precursor protein. This activation mechanism has been suggested to be similar to the cysteine switch mechanism as proposed for matrix metalloproteinases (MMPs) (Grams et al, 1993). Although there are a large number of studies dealing with snake venoms, no report of the metalloproteinase has been found from the Duvernoy's gland of Rabdophis tigrinus tigrinus.…”

Section: Introductionmentioning

confidence: 71%

Characterization of a Novel Metalloproteinase in Duvernoy's Gland of Rhabdophis Tigrinus Tigrinus

et al. 2006

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-During the characterization of hemorrhagic factor in venom of Rhabdophis tigrinus tigrinus, so-called Yamakagashi in Japan, one of the Colubridae family, a novel metalloproteinase with molecular weight of 38 kDa in the Duvernoy's gland of Yamakagashi was identified by gelatin zymography and by monitoring its proteolytic activity using a fluorescence peptide substrate, MOCAc-PLGLA 2 pr(Dnp)AR-NH 2 , which was developed for measuring the well-known matrix metalloproteinase (MMP) activity.After purification by gel filtration HPLC and/or column switch HPLC system consisting of an affinity column, which was immobilized with a synthetic BS-10 peptide (MQKPRCGVPD) originating from propeptide domain of MMP-7 and a reversed-phase column, the N-terminal amino acid sequence of the 38 kDa metalloproteinase was identified as FNTFPGDLK which shared a high homology to Xenopus MMP-9.The 38 kDa metalloproteinase required Zn 2+ and Ca 2+ ions for its proteolytic activity. In addition, the proteolytic activity was almost completely inhibited by BS-10, a MMP inhibitor, but not by the serine proteinase inhibitors, cysteine proteinase inhibitors and aspartic proteinase inhibitors.Together these results demonstrated that the 38 kDa proteinase is a novel snake verom metalloproteinase (SVMP) containing HExGHxxGxxH motif which possesses high affinity to the BS-10 peptide, into its molecule, and the enzymatic properties are closed to that of MMPs.Based on the results obtained in the present study, we concluded that the 38 kDa metalloproteinase is a novel metalloproteinase whose activity may be regulated by the cysteine switch mechanism, and could be classified as one of the matrix metalloproteinases rather than snake venom metalloproteinases.

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Section: Introductionmentioning

confidence: 71%

Characterization of a Novel Metalloproteinase in Duvernoy's Gland of Rhabdophis Tigrinus Tigrinus

et al. 2006

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“…Similarly, as in the matrix metalloproteinases, a cysteine-switch mechanism has been proposed for these enzymes (Hite et al, 1992;Grams et al, 1994).…”

Section: Proenzyme Activationmentioning

confidence: 97%

The metzincins — Topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a super family of zinc‐peptidases

et al. 1995

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The three-dimensional structures of the zinc endopeptidases human neutrophil collagenase, adamalysin I1 from rattle snake venom, alkaline proteinase from Pseudomonas aeruginosa, and astacin from crayfish are topologically similar, with respect to a five-stranded 0-sheet and three a-helices arranged in typical sequential order. The four proteins exhibit the characteristic consensus motif HEXXHXXGXXH, whose three histidine residues are involved in binding of the catalytically essential zinc ion. Moreover, they all share a conserved methionine residue beneath the active site metal as part of a superimposable "Met-turn.'' This structural relationship is supported by a sequence alignment performed on the basis of topological equivalence showing faint but distinct sequential similarity. The alkaline proteinase is about equally distant (26% sequence identity) to both human neutrophil collagenase and astacin and a little further away from adamalysin I1 (17% identity). The pairs astacin/adamalysin 11, astacidhuman neutrophil collagenase, and adamalysin Whuman neutrophil collagenase exhibit sequence identities of 16%, 14%, and 13%, respectively. Therefore, the corresponding four distinct families of zinc peptidases, the astacins, the matrix metalloproteinases (matrixins, collagenases), the adamalysins/reprolysins (snake venom proteinases/reproductive tract proteins), and the serralysins (large bacterial proteases from Serratia, Erwinia, and Pseudomonas) appear to have originated by divergent evolution from a common ancestor and form a superfamily of proteolytic enzymes for which the designation "metzincins" has been proposed. There is also a faint but significant structural relationship of the metzincins to the thermolysin-like enzymes, which share the truncated zincbinding motif HEXXH and, moreover, similar topologies in their N-terminal domains.Keywords: crystal structure; metalloproteinase; molecular evolution; protein family; sequence alignment; topology is involved in metal binding (McKerrow, 1987;

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“…3,4 The inactive TACE of 120 kDa protein is removed in the N-terminus prodomain and then converted to the active form of 100 kDa protein by furin in vivo. 5,6 To determine the catalytic capacity of transgene-derived TACE, the tissue lysates of skin from TACE-Tg and WT mice were incubated with furin in vitro.…”

Section: No Spontaneous Phenotype In Tace-tg Micementioning

confidence: 99%

“…1,2 Initially produced as an inactive 120 kDa protein, the N-terminus prodomain is removed by furin at the trans-golgi network, and consequently TACE is converted to an active form of 100 kDa protein. [3][4][5][6] The active form of TACE is transported to the plasma membrane and binds to its substrates on the cell surface. Substrates of TACE include TNF-a, TNF receptors, and epidermal growth factor receptor (EGFR) ligands.…”

mentioning

confidence: 99%

Overexpression of TNF-α-converting enzyme in fibroblasts augments dermal fibrosis after inflammation

Fukaya

Matsui

Tomaru

et al. 2013

Laboratory Investigation

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TNF-a-converting enzyme (TACE) can cleave transmembrane proteins, such as TNF-a, TNF receptors, and epidermal growth factor receptor (EGFR) ligands, to release the extracellular domains from the cell surface. Recent studies have suggested that overexpression of TACE may be associated with the pathogenesis of inflammation and fibrosis. To determine the roles of TACE in inflammation and fibrosis, TACE transgenic (TACE-Tg) mice, which overexpressed TACE systemically, were generated. As the transgene-derived TACE was expressed as an inactive form, no spontaneous phenotype developed in TACE-Tg mice. However, the transgene-derived TACE could be converted to an active form by furin in vitro and by phorbol myristate acetate (PMA) in vivo. Subcutaneous injection of PMA into mice induced inflammatory cell infiltration 1 day later and subsequent dermal fibrosis 7 days later. Interestingly, the degree of dermal fibrosis at day 7 was significantly higher in TACE-Tg mice than in wild-type mice. Correspondingly, PMA increased the expression of type I collagen in the primary culture of dermal fibroblasts derived from TACE-Tg mice. Furthermore, phosphorylated EGFR was increased in the fibroblasts by the PMA treatment. The collective findings suggest that TACE overexpression and activation in fibroblasts could shed off putative EGFR ligands. Subsequently, the soluble EGFR ligands could bind and activate EGFR on fibroblasts, and then increase the type I collagen expression resulting in induction of dermal fibrosis. These results also suggest that TACE and EGFR on fibroblasts may be novel therapeutic targets of dermal fibrosis, which is induced after diverse inflammatory disorders of the skin. KEYWORDS: EGFR; fibrosis; inflammation; PMA; TACE TNF-a-converting enzyme (TACE), which belongs to a disintegrin and metalloproteinase (ADAM) family, can cleave transmembrane proteins to release the extracellular domains from the cell surface. 1,2 Initially produced as an inactive 120 kDa protein, the N-terminus prodomain is removed by furin at the trans-golgi network, and consequently TACE is converted to an active form of 100 kDa protein. [3][4][5][6] The active form of TACE is transported to the plasma membrane and binds to its substrates on the cell surface. Substrates of TACE include TNF-a, TNF receptors, and epidermal growth factor receptor (EGFR) ligands.When focusing on the role of TNF-a in inflammation, it is considered that TACE contributes to promote inflammation by increasing soluble TNF-a. However, it is also considered that TACE plays a role in the suppression of inflammation by decreasing membrane-type TNF receptors and producing soluble TNF receptors, which can work as decoy receptors. These concepts seem contradictory, but TACE really functions to maintain the physiological homeostasis. The expression of TACE substrates is strictly regulated in a timedependent manner during the inflammation process.On the other hand, it has been demonstrated that rat collagen antibody-induced arthritis and lipopolysaccharide (LPS)-induced acu...

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Activation of snake venom metalloproteinases by a cysteine switch‐like mechanism

Cited by 114 publications

References 30 publications

Characterization of a Novel Metalloproteinase in Duvernoy's Gland of Rhabdophis Tigrinus Tigrinus

Characterization of a Novel Metalloproteinase in Duvernoy's Gland of Rhabdophis Tigrinus Tigrinus

The metzincins — Topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a super family of zinc‐peptidases

Overexpression of TNF-α-converting enzyme in fibroblasts augments dermal fibrosis after inflammation

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