Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of serine protease inhibitors, diisopropyl fluorophosphate (DFP) and phenylmethanesulfonyl fluoride (PMSF), on hemolytic activity of C6 were reinvestigated. C6 was inactivated in a range of 1-10 mM by both of the inhibitors as previously reported. Limited proteolytic digestion was also studied to elucidate the functional and structural domains of C6. The major fragments produced by trypsin, plasmin, or lysyl endopeptidase could not be separated unless disulfide bonds were disrupted, but Staphylococcus aureus V8 protease yielded several fragments, each of which was not linked by disulfide bond. When C6 labeled with [3H]DFP was subjected to limited digestion with V8 protease, a fragment with a molecular weight of 38 kilodaltons (kDa) was mainly labeled and other fragments of 53 kDa and 26.4 kDa were also faintly labeled, while fragment 35 kDa wasn't labeled, indicating specific domains reactive with DFP. On the other hand, when C6 with or without DFP treatment was digested with V8 protease and those fragments were incubated with C5 and subjected to sucrose density ultracentrifugation, fragments 53, 38, 35 and 27.5 kDa interacted with C5 in both cases. These results suggest that C6 modified by DFP can interact with C5, and the amino-terminal sequences of fragment 38 and 35 kDa suggest the binding domain of C6 with C5 takes place within the two short consensus repeats.
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PMID:Functional and structural domains of the sixth component (C6) of human complement. 205 69

The pro-inflammatory cytokines IL-1 and TNF-alpha are primary mediators of the acute phase response, the complex reaction of the mammalian organism to infection and injury. Among the genes activated by TNF-alpha and IL-1 in a variety of cells is TNF-stimulated gene 6 (TSG-6). The TSG-6 cDNA encodes a secreted 35 kDa glycoprotein which is abundant in synovial fluids of patients with various forms of arthritis and detectable in serum of patients with different inflammatory or autoimmune disorders. TSG-6 protein consists of two structural domains: a hyaluronan-binding link module, the characteristic domain of the hyaladherin family of proteins, and a C-terminal CUB domain, present in a variety of diverse proteins. TSG-6 forms a stable complex with components of the plasma protein inter-alpha-inhibitor (I[alpha]I), a Kunitz-type serine protease inhibitor. TSG-6 and I(alpha)I synergize to inhibit plasmin, a serine protease involved in the activation of matrix metalloproteinases which are part of the proteolytic cascade associated with inflammation. Recombinant human TSG-6 protein exerts a potent anti-inflammatory effect in a murine model of acute inflammation. Modulation of the proteolytic network associated with inflammatory processes may be a mechanism whereby TSG-6, in cooperation with I(alpha)I, inhibits inflammation. Activation of the TSG-6 gene by pro-inflammatory cytokines, presence of TSG-6 protein in inflammatory lesions and its anti-inflammatory effect suggest a role for TSG-6 in a negative feed-back control of the inflammatory response.
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PMID:TSG-6: an IL-1/TNF-inducible protein with anti-inflammatory activity. 924 9

The biochemical mechanism controlling nucleation of mineral crystals in developing bone, along with the growth and propagation of these crystals once formed, remains poorly understood. To define the nucleation mechanism, a proteomics analysis was begun on isolated biomineralization foci (BMF), sites of initial crystal nucleation in osteoblastic cell cultures and in primary bone. Comparative analyses of the protein profile for mineralized BMF with that for total osteoblast cultures revealed the latter were enriched in several proteins including BAG-75 and BSP, as well as fragments of each. When 12 protease inhibitors were added separately to UMR 106-01 osteoblastic cultures, only the serine protease inhibitor 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) blocked cleavage of BAG-75 and BSP, and prevented mineral crystal nucleation within BMF. Consideration of the specificities of the inhibitors tested and the fact that AEBSF inhibition was not dependent upon inclusion of FBS in the culture media indicated that mineral nucleation does not require serine protease plasmin, thrombin, kallikrein, urokinase, C1s or furin. In contrast, SKI-1 (S1P or site-1) is a membrane-bound serine protease inhibitable by AEBSF. We show here for the first time that mineralizing UMR 106 cells express a 98-kDa active, soluble form of SKI-1 within BMF. In contrast, nonmineralizing UMR cells appear to differentially process SKI-1 into smaller immunoreactive fragments (<35 kDa). These findings suggest that SKI-1 plays a direct or indirect role in assembly of functional nucleation complexes containing BAG-75 and BSP and their fragments, thus facilitating initial mineral nucleation within these biomineralization foci.
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PMID:Potential role of proprotein convertase SKI-1 in the mineralization of primary bone. 1872 45