Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During neurosurgery the freshly secreted extracellular fluid (ECF) from the choroid plexus was sampled with small pieces of application paper in three patients with intractable epilepsy. The samples were analyzed for free amino acids and for soluble proteins. The results were compared with corresponding data on extracellular fluid from the brain surface obtained with dialysis-perfusion as well as with the cerebrospinal fluid (CSF) acquired by lumbar punction. The dialysis data were calibrated against the paper results. The choroid plexus secretion had a high concentration of transthyretin as well as of an unidentified protein with an isoelectric point of 7.4. The cortical ECF exhibited high concentrations of tau-globulin and gamma-trace protein. Among the amino acids, glutamine had lower concentration in the choroid plexus secretion and higher concentrations in the ECF of the brain compared to the CSF. The amino acid derivative ethanolamine exhibited a similar pattern. This was interpreted to demonstrate that these compounds enter the CSF from the brain tissue. In contrast, alanine, serine, and taurine had a lower concentration in the CSF than in the plexus secretion which suggests that they are removed from the CSF by brain tissue.
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PMID:The contribution from the choroid plexus and the periventricular CNS to amino acids and proteins in the human CSF. 169 75

The interaction between recombinant human cystatin C and the cysteine proteinases papain and actinidin was studied by spectroscopic, kinetic and equilibrium methods. The absorption, near-u.v.c.d. and fluorescence-emission difference spectra for the cystatin C-proteinase interactions were all found to be similar to the corresponding spectra for chicken cystatin. The kinetics of binding of cystatin C to the two enzymes were best described by a simple reversible one-step bimolecular mechanism, like the kinetics of the reaction of chicken cystatin with several cysteine proteinases. Moreover, the second-order association rate constants at 25 degrees C, pH 7.4 and I0.15, of 1.1 x 10(7) and 2.4 x 10(6) M-1.s-1 for the reactions of cystatin C with papain and actinidin respectively, were similar to the corresponding rate constants for the chicken inhibitor and close to the value expected for a diffusion-controlled rate. The dissociation equilibrium constants, approx. 11 fM and approx. 19 nM for the binding of cystatin C to papain and actinidin respectively, were also comparable with the dissociation constants for chicken cystatin. The affinity between cystatin C and several inactivated papains or actinidins decreased with increasing size of the inactivating group in a manner similar to that in earlier studies with the chicken inhibitor. Together, these results strongly indicate that the mechanisms of the reactions of cystatin C and chicken cystatin with cysteine proteinases are identical or highly similar, but differ from that of reactions between serine-proteinase inhibitors and their target enzymes. The model for the proteinase-inhibitor interaction, based on the X-ray structure of chicken cystatin, therefore should be largely applicable also to human cystatin C.
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PMID:Interaction of recombinant human cystatin C with the cysteine proteinases papain and actinidin. 173 67

The effect of four human serine proteinases on the human cysteine proteinase inhibitor, cystatin C, has been studied in vitro. Neutrophil elastase in catalytic amounts was observed to rapidly cleave cystatin C at neutral pH, thereby giving rise to a modified form of the inhibitor lacking the N-terminal Ser1-Val10 decapeptide. The two other leukocyte serine proteinases, cathepsin G and neutrophil proteinase 4, did not catalytically hydrolyse cystatin C bonds. Neither had the seminal plasma serine proteinase, prostate-specific antigen, any effect on cystatin C. The physiological implications of neutrophil elastase catalysed modification of cystatin C are discussed, and recent findings indicating that this reaction also occurs in vivo are reviewed.
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PMID:Regulation of cystatin C activity by serine proteinases. 180 27

mRNA from a postmortem liver sample of a patient with classical phenylketonuria was examined using the chemical cleavage of mismatch (CCM) method to search for mutations in phenylalanine hydroxylase. Initial screening identified a heterozygous alteration in exon 2 which changed the encoded amino acid from phenylalanine (TTC) to leucine (TTG) at codon 39 and a polymorphism at codon 430 where the change from CTG to CTC did not alter the encoded leucine. Use of the CCM technique also revealed that the control reference clone differed from the published sequence by having a substitution of isoleucine (ATT) for methionine (ATG) at codon 276 and CAA rather than CAG as the codon for glutamine 232. By using the mRNA from the patient instead of the control as the source for the radiolabeled probe for the CCM technique, a second previously undetected alteration was identified in exon 10 where the change from TCA to CCA at codon 349 altered the amino acid from serine to arginine. Judicious choice of probes gives the CCM method the potential to detect close to 100% of single base mutations.
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PMID:Mutation detection in phenylketonuria by using chemical cleavage of mismatch: importance of using probes from both normal and patient samples. 206 69

Peptides spanning the entire, or part of, the Gly4-Glu21 segment of the human cysteine proteinase inhibitor cystatin C have been synthesized. Peptides containing residues on the N-terminal side of Gly11 were rapidly cleaved by papain at the bond Gly11-Gly12 whereas a peptide starting at residue Gly11 was not, thus demonstrating 1. that the N-terminal segment of cystatin C has an amino acid sequence that would allow rapid interaction between this segment and the substrate pocket of papain and, if this interaction takes place, that 2. the cystatin C residue Gly11 would be in the P1 position, and 3. the major interaction would be between residues Arg8-Val10 and the papain substrate pocket subsites S4, S3 and S2, respectively. Several modified peptide derivatives containing either diazomethane groups or peptide bond isosters were synthesized based on the structure of the Leu9-Gly11 segment of cystatin C and tested for their cysteine proteinase inhibiting capacity. The peptidyl derivatives, t-butyloxycarbonyl-valyl-glycyl-diazomethane and benzyloxycarbonyl-leucyl-valyl-glycyl-diazomethane irreversible inhibited the cysteine proteinases papain, bovine cathepsin B and streptococcal proteinase, but did not influence the activity of serine, aspartic or metallo-proteinases.
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PMID:Synthesis of cysteine proteinase inhibitors structurally based on the proteinase interacting N-terminal region of human cystatin C. 240 May 74

We describe the cloning and the DNA sequence of the Escherichia coli supH missense suppressor and of the supD60(Am) suppressor genes. supH is a mutant form of serU which codes for tRNASer2. The supH coding sequence differs from the wild-type sequence by a single nucleotide change which corresponds to the middle position of the anticodon. The CGA anticodon of wild-type tRNA and CUA anticodon of supD tRNA is changed to CAA in supH tRNA, which is expected to recognize the UUG leucine codon. We propose that the supH suppressor causes the insertion of serine in response to this codon. The temperature sensitivity caused by supH may be due to a conformation of the CAA anticodon in the supH tRNASer that is slightly different than that in the corresponding tRNALeu species.
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PMID:Escherichia coli supH suppressor: temperature-sensitive missense suppression caused by an anticodon change in tRNASer2. 315 15

The 5' context of 671 Escherichia coli stop codons UGA and UAA has been compared with the context of stop-like codons (UAC, UAU and CAA for UAA; UGG, UGC, UGU and CGA for UGA). We have observed highly significant deviations from the expected nucleotide distribution: adenine is over-represented whereas pyrimidines are under-represented in position -2 upstream from UAA. Uridine is over-represented in position -3 upstream from UGA. Lysine codons are preferable immediately prior to UAA. A complete set of codons for serine and the phenylalanine UUC codon are preferable immediately 5' to UGA. This non-random codon distribution before stop codons could be considered as a molecular device for modulation of translation termination. We have found that certain fragment of E. coli release factor 2 (RF2) (amino acids 93-114) is similar to the amino acid sequences of seryl-tRNA synthetase (positions 10-19 and 80-93) and of beta (small) subunit (positions 72-94) of phenylalanyl-tRNA synthetase from E. coli. Three-dimensional structure of E. coli seryl-tRNA synthetase is known [1]: Its N-terminus represents an antiparallel alpha-helical coiled-coil domain and contains a region homologous to RF2. On the basis of the above-mentioned results we assume that a specific interaction between RF2 and the last peptidyl-tRNA(Ser/Phe) occurs during polypeptide chain termination in prokaryotic ribosomes.
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PMID:Termination of translation in bacteria may be modulated via specific interaction between peptide chain release factor 2 and the last peptidyl-tRNA(Ser/Phe). 833 98

The effect of different protease inhibitors on the proteolytic processing of the plum pox potyvirus (PPV) polyprotein has been analyzed. Human cystatin C, an inhibitor of cysteine proteases, interfered with the autoprocessing of the viral papain-like cysteine protease HCPro. Unexpectedly, it also had an inhibitory effect on the autocatalytic cleavage of the Nla protease which, although it has a Cys residue in its active center, has been described as structurally related to serine proteases. Other protease inhibitors tested had no effect on any of the cleavage events analyzed.
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PMID:Inhibitory effects of human cystatin C on plum pox potyvirus proteases. 834 5

African trypanosomes contain proteases that may be released into the bloodstream of their infected hosts. This paper describes a novel, combined isolation of a cysteine proteinase (called trypanopain-Tb) and a serine oligopeptidase (which we call oligopeptidase-Tb) from Trypanosoma brucei brucei, as well as a comparison of the activities of these two enzymes against several host regulatory molecules. The enzymes differed in various respects. Firstly, purified trypanopain-Tb was shown to readily cleave proteins such as gelatin maximally at acidic pH. In contrast, oligopeptidase-Tb, which is optimally active at alkaline pH, did not hydrolyse proteins larger than 4 kDa. However, it readily hydrolysed various polypeptides, including neurotensin and atrial natriuretic factor. The interaction of the two enzymes with mammalian protease inhibitors also differed. Cystatins and alpha2-macroglobulin effectively inhibited trypanopain-Tb, with the Ki values for cystatin C and low-molecular-mass kininogen (approximately 10(-11) M) predicting, that trypanopain-Tb is likely to be effectively controlled by these inhibitors if released into the host bloodstream. In contrast, oligopeptidase-Tb was not inhibited by serpins or (a2-macroglobulin, suggesting that it may remain active if released into the host bloodstream. In support of these in vitro results, the blood of trypanosome-infected rats displayed no trypanopain-Tb-like activity, but exhibited high oligopeptidase-Tb-like activity. Thus, while trypanopain-Tb seems likely to be confined to an intracellular role within the parasite, oligopeptidase-Tb has the potential to remain active in the host bloodstream and so contribute directly to pathogenesis.
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PMID:Proteases from Trypanosoma brucei brucei. Purification, characterisation and interactions with host regulatory molecules. 870 74

The implantation of the mouse embryo requires the controlled invasion of the uterine stroma by the embryonic trophoblast. This event is dependent, in part, on the secretion of matrix metalloproteinases and serine proteinases for the extracellular degradation of the uterine matrix. Proteinase activity is controlled by stromal decidualization and specific proteinase inhibitors. This work adds to our understanding of implantation and placentation by reporting the expression and function of another class of proteinases/inhibitors closely related to invasive cell behavior. We focused on the cysteine proteinases, cathepsins B and L, and their inhibitor cystatin C. Northern blots showed that trophoblast expressed cathepsin B throughout the invasive period (days 5.5-10.5). Both cathepsin B message and cathepsin L protein were localized to the mature, invasive trophoblast giant cells. Substrate gel electrophoresis showed an increase in giant cell cathepsin activity with enzyme profiles changing at the end of the invasive period. Northern and western blotting showed that cystatin C, the main inhibitor of cathepsins, was a major product of the decidualizing stroma. Message levels first increased in peripheral decidualizing cells, with the protein localizing close to the embryo during implantation (days 5.5-8.5). With the regression of the decidua beginning on day 9.5, a coordinated upregulation of both cathepsin B and cystatin C was observed implying a role for controlled cathepsin expression during apoptosis. E-64, a synthetic inhibitor of cathepsins B and L, was injected into pregnant females at the stage of blastocyst attachment (days 4.5-5.5). High doses resulted in the complete failure of implantation while lower doses resulted in stunted embryos and a reduced decidual reaction. These results suggested that cathepsins B and L are necessary for normal embryo development and uterine decidualization, and that decidua contributes to their control by a coordinated expression of cystatin C within the implantation site.
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PMID:The expression and function of cystatin C and cathepsin B and cathepsin L during mouse embryo implantation and placentation. 931 Mar 36


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