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)

A highly purified preparation of human properdin (P) has been obtained in a simple two-step procedure utilizing reversed application of the technique of affinity chromatography. The method involved precipitation of properdin from human serum and subsequent passage through an immunoadsorbent column of Sepharose anti-RP globulin which bound the contaminating proteins. The immunochemical properties of the isolated properdin (P) was found to be different from those of activated properdin (P). P was shown to be a 6.1S, beta2 globulin with a mean subunit m.w. of 57,900. P on the other hand was a 5.1S protein with gamma2 mobility and a subunit m.w. of 53,000 daltons. Double diffusion analysis using anti-P revealed a reaction of identity between P and P. However, when the reaction was developed with anti-P, a reaction of partial identity was obtained and the precipitin line of P was seen to spur over the line developed with P. Mild treatment with plasmin or trypsin converted P to P. Unlike P, P was ineffective in triggering the activation of the Properdin System in RP unless trace amounts of zymosan were added. Under these conditions P was found to be converted to P. The results indicate that properdin is present in fresh serum in a precursor form and its activation to P involves a limited proteolytic cleavage of the molecule.
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PMID:Purification of native properdin by reversed affinity chromatography and its activation by proteolytic enzymes. 95 Apr 61

Proteolysis has a critical role in defining the typical organoleptic characteristics of Grana Padano, a well-known Italian cheese. During the ripening process, hydrolysis of beta-casein produces different fragments, the most abundant and widely studied of which are gamma-caseins, three polypeptides containing the HOOC-terminal portion of beta-casein. By sodium dodecyl sulfate-PAGE and a specific anti-beta-casein monoclonal antibody, two beta-casein-derived bands were identified in Grana Padano cheese: betaa and betab. Thanks to the identification of the amino acid sequences, it was shown that: a) betaa contains gamma1-casein [beta-casein (29-209)] and the correlated peptide [beta-casein (30-209)]; b) betab contains gamma2-casein [beta-casein (106-209)] and gamma3-casein [beta-casein (108-209)]. The production of betaa and betab by the three enzymes most involved in cheese proteolysis (pepsin, chymosin, and plasmin) was evaluated by performing in vitro digestions. A significant correlation between abundance of some polypeptides and ripening process was shown.
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PMID:Proteolysis of beta-casein as a marker of Grana Padano cheese ripening. 1121 50

Cancer cell invasion is facilitated by extracellular matrix degrading proteases such as plasmin. We have studied the expression of plasminogen activator inhibitor-1 (PAI-1) and urokinase receptor (uPAR) together with the gamma2-chain of laminin-5 (lam-gamma2) by immunohistochemistry in 20 cases with incipient oral squamous cell carcinoma (SCC). PAI-1-positive neoplastic cells located at the tip of the putative invasive front of grade 1 (incipient) carcinoma were seen in 16 of the 20 cases (75%), whereas adjacent normal and dysplastic epithelium was PAI-1-negative. Clusters of putative invasive neoplastic cells located in the lamina propria were PAI-1-positive in areas with grade 2 incipient carcinoma as were invasive cancer cells in areas of grade 3-4 invasive carcinoma. uPAR immunoreactivity was strongly expressed in numerous stromal cells in the carcinoma area in all 20 lesions, while a few uPAR-positive stromal cells were found in areas with normal and dysplastic epithelium. uPAR-positive neoplastic cell islands located at the front of the lesions were seen in 15 of the 20 cases. The expression pattern of lam-gamma2 was very similar to that of PAI-1; however, lam-gamma2-positive neoplastic cells were only detected in 11 of the 20 cases (55%) in areas of grade 1 incipient carcinoma. Direct comparison of the 3 components revealed colocalization in neoplastic cell islands in both incipient and invasive SCC. Our results suggest that PAI-1 is a novel potential marker of initial invasion in oral SCC, and that the coordinated expression of PAI-1 with uPAR and lam-gamma2 sustain the features of the early invasive cancer cells.
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PMID:Expression of plasminogen activator inhibitor-1, urokinase receptor and laminin gamma-2 chain is an early coordinated event in incipient oral squamous cell carcinoma. 1639 14

To determine the significance of the gamma2 calcium-binding site in fibrin polymerization, we synthesized the fibrinogen variant, gammaD298,301A. We expected these two alanine substitutions to prevent calcium binding in the gamma2 site. We examined the influence of calcium on the polymerization of gammaD298,301A fibrinogen, evaluated its plasmin susceptibility, and solved 2.7 and 2.4 A crystal structures of the variant with the peptide ligands Gly-Pro-Arg-Pro-amide (GPRP) and Gly-His-Arg-Pro-amide (GHRP), respectively. We found that thrombin-catalyzed polymerization of gammaD298,301A fibrinogen was modestly impaired, whereas batroxobin-catalyzed polymerization was significantly impaired relative to normal fibrinogen. Notably, the influence of calcium on polymerization was the same for the variant and for normal fibrinogen. Fibrinogen gammaD298,301A was more susceptible to plasmin proteolysis in the presence of GPRP. This finding suggests structural changes in the near-by "a" polymerization site. Comparisons of the structures revealed minor conformational changes in the gamma294-301 loop that are likely responsible for the weakened "a" site. When considered altogether, the data suggest that the gamma2 calcium-binding site does not significantly modulate polymerization. We cannot, however, rule out the possibility that the weakened "a" polymerization site masks an important role for the gamma2 calcium-binding site in normal polymerization. Somewhat unexpectedly, the structure data showed that GPRP bound to the "b" site and induced the same local conformational changes as GHRP to this site. This structure shows that "A:b" interactions can occur and suggests that these may participate in normal polymerization.
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PMID:Probing the gamma2 calcium-binding site: studies with gammaD298,301A fibrinogen reveal changes in the gamma294-301 loop that alter the integrity of the "a" polymerization site. 1741 Oct 74