CA-MMP: a matrix metalloproteinase with a novel cysteine array, but without the classic cysteine switch.
A matrix metalloproteinase (MMP)-like gene was identified in mouse to contain a conserved MMP catalytic domain and an RRRR motif. It lacks a classic cysteine switch, but it possesses two novel motifs: a cysteine array (Cys-X(6)-Cys-X(8)-Cys-X(10)-Cys-X(3)-Cys-X(2)-Cys), and a novel Ig-fold. It is named CA-MMP after the distinct cysteine array motif, and little is known about its biochemical function. In an attempt to characterize CA-MMP activity, the full-length sequence was expressed in mammalian cells and its product found to be cell-associated without detectable secretion. In light of this unusual finding, a chimera combining the catalytic domain of CA-MMP with the prodomain of stromelysin-3 was constructed to express a fully active enzyme in mammalian cells. Purified CA-MMP catalytic domain expresses proteolytic activity against protein substrates in an MMP inhibitor sensitive fashion. Taken together, it is concluded that CA-MMP is an MMP with distinct structure, biochemical properties and evolutionary history that may define a new subclass of the MMP superfamily.
Pei
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Department of Pharmacology, 3-249 Millard Hall, 435 Delaware St. S.E. ,University of Minnesota, Minneapolis, MN, USA. peixx003@tc.umn.edu
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D003001:Cloning, Molecular; D003545:Cysteine / Q000737:chemistry*; D018076:DNA, Complementary / Q000032:analysis; D004622:Embryo, Mammalian / Q000201:enzymology; D005091:Exons; D005109:Extracellular Matrix / Q000201:enzymology; D007438:Introns; D053508:Matrix Metalloproteinase 12; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; C121434:CA-matrix metalloproteinases; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases; D053508:Matrix Metalloproteinase 12; D003545:Cysteine