Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The protease inhibitors Trasylol and soyabean trypsin inhibitor prevented the activation of plasma inactive renin by acid. 2. N-Ethylmaleimide inhibited acid-activation to some extent but o-phenathroline had no effect. 3. Acid-activation of the inactive renin in human plasma is mediated by a serine protease.
Clin Sci Mol Med Suppl 1978 Dec
PMID:An endogenous protease activating plasma inactive renin. 3 3

1. We have found that 'acid'-activation of inactive human plasma renin is a two-phase process. About 30% of activation occurs during dialysis to pH 3.3; the remaining 70% occurs at alkaline pH. 2. The 'alkaline phase' of activation has a pH optimum between 7.5 and 8.4. It is inhibited by unacidified plasma and by soya-bean or lima-bean trypsin inhibitors. 3. 'Cryoactivation' of inactive plasma renin, which occurs at -4 degrees C and alkaline pH, is also inhibited by soya-bean or lima-bean trypsin inhibitors and by the serine protease inhibitors diisopropylphosphorofluoridate and benzamidine. 4. Thus endogenous neutral serine proteases participate in the activation of inactive plasma renin in vitro. Their action is prevented in the circulation by inhibitors which are inactivated by acid or cold.
Clin Sci Mol Med Suppl 1978 Dec
PMID:Activation of inactive plasma renin: evidence that both cryoactivation and acid-activation work by liberating a neutral serine protease from endogenous inhibitors. 3 4

A Bacillus subtilis intracellular serine protease is homologous in sequence to an extracellular serine protease from the same strain, indicating the presence of two related structural genes in the Bacillus subtilis genome.
Mol Gen Genet 1978 Feb 27
PMID:Two related structural genes coding two homologous serine proteases in the Bacillus subtilis genome. 41 38

The N-terminal pro-peptide of 77 amino acid residues is essential for the folding of subtilisin, an alkaline serine protease from Bacillus subtilis. The synthetic pro-peptide has been shown to be capable of guiding the proper folding of denatured subtilisin to enzymatically active enzyme. Thus the pro-peptide serves as an intramolecular chaperone, which is removed by an autoprocessing reaction after the completion of the folding. With use of localized polymerase chain reaction random mutagenesis a total of 25 amino acid substitution mutations that affected subtilisin activities were isolated. These mutations occurred in a high frequency at the hydrophobic regions of the pro-peptide. For one of the mutations, M(-60)T, a second-site suppressor mutation, S(188)L, was isolated within the mature region. These results suggest that the pro-peptide consists of a few functional regions which interact with specific regions of the mature region of subtilisin during the folding process.
J Mol Biol 1992 Aug 20
PMID:Functional analysis of the intramolecular chaperone. Mutational hot spots in the subtilisin pro-peptide and a second-site suppressor mutation within the subtilisin molecule. 135 66

C1r is a Ca(2+)-binding serine protease that interacts with two other plasma proteins, C1q and C1s, to form C1, the first component of the complement cascade. A monoclonal antibody, BG6, has been produced which binds to C1r only in the presence of Ca2+, requiring 3-5 microM Ca2+ for half-maximal binding. The antibody reacts with native and heat-denatured C1r, and with zymogen C1r, but does not cross-react with C1s or C1q. BG6 did not significantly affect the esterolytic activity of C1r toward a synthetic thioester substrate nor the hemolytic activity of C1 reconstituted from subcomponents in the presence of the antibody. A tryptic fragment of C1r which consists of the C-terminal gamma region of the A chain disulfide-linked to the B chain (gamma B) binds in a Ca(2+)-dependent manner to BG6-Sepharose. Western blotting experiments have further localized the epitope to the gamma region of the A chain, which is composed of two short consensus repeat (SCR) units. The N-terminal alpha region contains the only previously determined Ca(2+)-binding site in the C1r molecule. Equilibrium dialysis experiments confirmed that C1r-gamma B does not bind Ca2+, and showed that antibody BG6 and the gamma B/BG6 complex do bind Ca2+. Thus, the Ca(2+)-dependent nature of this interaction is due exclusively to binding of the metal ion to the antibody. Equilibrium dialysis and immunoblotting have further localized the Ca(2+)-binding site to the Fab fragment of BG6, indicating that the metal-induced conformational change residues in or near the variable region of the IgG. BG6 may set a precedent for the preparation of Ca(2+)-dependent antibodies to non-Ca(2+)-binding epitopes in other proteins.
Mol Immunol 1992 Jan
PMID:A calcium-binding monoclonal antibody that recognizes a non-calcium-binding epitope in the short consensus repeat units (SCRs) of complement C1r. 137 May 72

The serine protease thrombin (E.C.3.4.21.5) is well recognized for its central role in hemostasis. In addition, thrombin is unique among the enzymes participating in the clotting cascade, by virtue of its cell activation effects induced via the enzymatic pocket or via functional domains located throughout the molecule. In this review, we elaborate on "nonhemostatic" activities of thrombin among which are interactions with vessel wall components. These activities include promotion of cellular adhesion and induction of smooth muscle cell proliferation. Thrombin can exert these effects when it is in a fluid phase and when it is immobilized to extracellular matrix.
Am J Respir Cell Mol Biol 1992 Feb
PMID:Thrombin as a multifunctional protein: induction of cell adhesion and proliferation. 154 Mar 75

Full elastolytic activity in Pseudomonas aeruginosa is a result of the combined activities of elastase, alkaline proteinase, and the lasA gene product, LasA. The results of this study demonstrate that an active fragment of the LasA protein which is isolated from the culture supernatant fraction is capable of degrading elastin in the absence of elastase, thus showing that LasA is a second elastase produced by this organism. In addition, it is shown that LasA-mediated enhancement of elastolysis results from the separate activities of LasA and elastase upon elastin. The LasA protein does not affect the secretion or activation of a proelastase as previously proposed in other studies. Furthermore, LasA has specific proteolytic capability, as demonstrated by its ability to cleave beta-casein. Preliminary analysis of beta-casein cleavage in the presence of various protease inhibitors suggests that LasA may be classified as a modified serine protease.
Mol Microbiol 1992 May
PMID:Further studies on Pseudomonas aeruginosa LasA: analysis of specificity. 158 15

The Kunitz-type protease inhibitor is one of the serine protease inhibitors. It is found in blood, saliva, and all tissues in mammals. Recently, a Kunitz-type sequence was found in the protein sequence of the amyloid beta precursor protein (beta APP). It is known that beta APP accumulates in the neuritic plaques and cerebrovascular deposits of patients with Alzheimer's disease. Collagen type VI in chicken also has an insertion of a Kunitz-type sequence. To elucidate the evolutionary origin of these insertion sequences, we constructed a phylogenetic tree by use of all the available sequences of Kunitz-type inhibitors. The tree shows that the ancestral gene of the Kunitz-type inhibitor appeared about 500 million years ago. Thereafter, this gene duplicated itself many times, and some of the duplicates were inserted into other protein-coding genes. During this process, the Kunitz-type sequence in the present beta APP gene diverged from its ancestral gene about 270 million years ago and was inserted into the gene soon after duplication. Although the function of the insertion sequences is unknown, our molecular evolutionary analysis shows that these insertion sequences in beta APP have an evolutionarily close relationship with the inter-alpha-trypsin inhibitor or trypstatin, which inhibits the activity of tryptase, a novel membrane-bound serine protease in human T4+ lymphocytes.
J Mol Evol 1992 Jun
PMID:Evolutionary origin of a Kunitz-type trypsin inhibitor domain inserted in the amyloid beta precursor protein of Alzheimer's disease. 159 45

The reaction center core of photosystem II, a multiprotein membrane bound complex, is composed of a heterodimer of two proteins, D1 and D2. A random mutagenesis technique was used to isolate a photosystem II deficient mutant, CP6t16, of the unicellular cyanobacterium, Synechocystis sp. PCC 6803. Nucleotide sequence analysis showed that the primary lesion in CP6t16 is an ochre mutation introducing a translational stop codon in the psbE gene, encoding the alpha-subunit of cytochrome b559, an integral component of the PSII complex. Analysis of the protein composition of CP6t16 thylakoid membranes isolated in the presence of serine protease inhibitors revealed that, in the absence of cytochrome b559, the D2 protein is also absent. However, the D1 protein is stably incorporated in these membranes, suggesting that the synthesis and integration of D1 are independent of those of D2 and cytochrome b559.
Mol Microbiol 1992 Apr
PMID:The D1 protein of the photosystem II reaction-centre complex accumulates in the absence of D2: analysis of a mutant of the cyanobacterium Synechocystis sp. PCC 6803 lacking cytochrome b559. 160 69

Cytolytic granules purified from natural killer lymphocytes (NK) contain a pore-forming protein (perforin) and a number of serine proteases. When these proteases are inhibited by serine protease-specific isocoumarin reagents the serine proteases are inactivated and the cytolytic activity of the granules is decreased. Paradoxically, it has been found that the general serine protease inhibitor phenylmethylsulfonyl fluoride (PMSF) frequently cannot block killing even though it inhibits many of the serine proteases. At the same time it has been reported that "purified" perforin alone can lyze cells. To address these inconsistencies we first compared the ability of PMSF and four new sulfonyl fluoride serine protease inhibitors to inhibit proteases and cell lysis. We determined the effects on lysis and the second order inhibition rate constants for five granule protease activities: ly-tryptase, ly-chymase, Met-ase (methionine cleaving), Ser-ase (serine cleaving) and Asp-ase (aspartic acid cleaving). One compound, 2-(Z-NH(CH2)2CONH)C6SO2F, was a potent inhibitor of Met-ase activity (k(obsd)/[I] = 162 M-1 s-1), ly-chymase activity (k(obsd)/[I] = 147 M-1 s-1), and granule-mediated as well as perforin-mediated lysis. PMSF was a poor inhibitor of granule proteases (k(obsd)/[I]'s less than 7 M-1 s-1 for four activities and no inhibition of Ser-ase); the lack of reactivity is consistent with the failure of PMSF to block granule lytic activity. We also prepared enriched perforin by anion exchange chromatography and showed that a ly-chymase and a Met-ase associated with perforin. By inhibiting these proteases we also inhibited lytic activity.
Mol Immunol 1992 Jun
PMID:Sulfonyl fluoride serine protease inhibitors inactivate RNK-16 lymphocyte granule proteases and reduce lysis by granule extracts and perforin. 160 92


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