Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pseudoxanthoma elasticum (PXE) is an inherited disease characterized by calcified degenerative changes of elastin in the skin, eye, and vasculature. Previous studies suggested the abnormal presence of a protease from PXE fibroblasts that degrades sulfated proteoglycans. This study describes the use of a radioassay to quantitate proteoglycan degradation by proteases from normal and PXE fibroblasts. PXE protease had optimal activity at pH 6.0. Inhibition of activity by 5 mM diisopropylfluorophosphate, 5 mM phenylmethylsulfonylfluoride, and 0.1 mM HgCl2 was reversed by 10 mM dithiothreitol. Iodoacetamide (1 mM) irreversibly inhibited activity. Carbobenzyloxy-phenylalanyl-alanyl (0.1 mM) and carbobenzyloxy-lysyl-diazomethyl ketone (10 microM) inhibited the proteoglycanase activity. These data suggest that the PXE proteolytic proteoglycanase activity is a cysteine protease. After blocking activity with 5 mM EDTA, addition of 10 mM Mg++, Mn++, Cu++, or Co++ had little effect (less than 10%) on restoring activity, 10 mM CaCl2 restored approximately 70% recovery of the activity, and 10 mM ZnCl2 stimulated the activity to 500% of the initial level. Similar normal fibroblast samples contained little zinc-dependent activity and a substantial amount of calcium-dependent activity. Thus the distinction between the divalent ion requirements for proteoglycan degradation suggests that the PXE fibroblasts may produce a different cysteine protease than do normal fibroblasts.
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PMID:Cysteine protease characteristics of the proteoglycanase activity from normal and pseudoxanthoma elasticum (PXE) fibroblasts. 635 May 11

The processing of culture medium of rabbit synovial fibroblasts led to the isolation of three stromelysin-1 (MMP-3) cleavage products: A 31-kDa protein, which represents a C-truncated latent stromelysin-1, an active stromelysin-1 of 21 kDa, that originates from the 31-kDa proform by activation. A third protein had a molecular mass of 25 kDa representing the C-terminal part of prostromelysin-1 and is missing in the C-truncated latent stromelysin-1. The activation process of human prostromelysin-1 in vitro is known to lead to an active stromelysin-1 with a relative molecular mass of 45 kDa by removing the N-terminal prodomain. This active stromelysin-1 is further processed to a lower molecular mass active form of 28 kDa. Our results obtained for the highly homologous rabbit stromelysin-1 indicate that another activation pathway is possible. In a first step prostromelysin-1 is hydrolysed between Met261-Glu generating a C-truncated latent stromelysin-1, which is activated by cleavage of the Thr83-Phe bond to the 21-kDa stromelysin-1. The latent C-truncated stromelysin-1 is slowly converted even at 4 degrees C into the active form. In the presence of 50 microM ZnCl2 this activation was prevented for at least three weeks. The activation rate is largely enhanced by aminophenylmercury acetate and especially by trypsin. The differences of the 21-kDa stromelysin-1 to a 28-kDa stromelysin-1 isolated from human rheumatoid synovial fluids described earlier are discussed.
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PMID:Isolation of latent 31-kDa C-truncated stromelysin and 21-kDa stromelysin from rabbit synovial fibroblasts: an alternative activation pathway for stromelysin. 806 May 32

Matrix metalloproteinases (MMPs) are involved in connective tissue turnover under physiological and pathological conditions. MMP activity is regulated by the requirement for zymogen activation. This report describes a proMMP-3 activator produced by articular cartilage. The activator initiates a step-wise processing of proMMP-3 to generate an array of active species. Sequencing of activation intermediates demonstrated cleavage on the NH2-terminal side of certain basic residues in the MMP-3 propeptide. Metal ion chelators inhibited activator-dependent proteolysis, and activity was restored by low levels of ZnCl2. These catalytic properties suggest similarity to members of the insulinase superfamily of metalloendopeptidases with in vitro specificity for single arginine or paired basic processing sites in a variety of prohormones. Dibasic sites also exist in the propeptides of several MMPs including proMMP-3. This is the first report that cartilage produces a potent MMP proenzyme activator, opening the possibility of a novel intrinsic activation pathway for catabolic processes in this avascular tissue.
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PMID:A matrix metalloproteinase proenzyme activator produced by articular cartilage. 964 25