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

Wild-type human cystatin C is directly involved in pathological fibrils formation, leading to hemorrhage, dementia and eventually death of people suffering from cerebral amyloid angiopathy. Some studies on cystatin C oligomerization have been already done but some points are still unclear. In order to learn more about this important process, we have investigated thermal and chemical (guanidine hydrochloride-induced) denaturation of human cystatin C. Studies performed using tryptophan fluorescence, calorimetry, circular dichroism and Fourier transform infrared spectroscopy demonstrate that neither chemical nor thermal denaturation of hCC are simple two-state events. One recognized intermediate form was dimeric cystatin C, whose appearance was preceded mainly by changes in the L2 binding loop. The other form occurred only in the chemical denaturation process and was characterized by partially recovered interactions maintaining the protein tertiary structure. Our studies also strongly indicate that the beta-structural motif of cystatin C is directly implicated in formation of temperature-induced aggregates.
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PMID:Thermal and guanidine hydrochloride-induced denaturation of human cystatin C. 1474 24

Studies show that administration of interferon (IFN)-alpha causes a significant increase in depressive symptoms. The enzyme indoleamine 2,3-dioxygenase (IDO), which converts tryptophan (TRP) into kynurenine (KYN) and which is stimulated by proinflammatory cytokines, may be implicated in the development of IFN-alpha-induced depressive symptoms, first by decreasing the TRP availability to the brain and second by the induction of the KYN pathway resulting in the production of neurotoxic metabolites. Sixteen patients with chronic hepatitis C, free of psychiatric disorders and eligible for IFN-alpha treatment, were recruited. Depressive symptoms were measured using the Montgomery Asberg Depression Rating Scale (MADRS). Measurements of TRP, amino acids competing with TRP for entrance through the blood-brain barrier, KYN and kynurenic acid (KA), a neuroprotective metabolite, were performed using high-performance liquid chromatography. All assessments were carried out at baseline and 1, 2, 4, 8, 12 and 24 weeks after treatment was initiated. The MADRS score significantly increased during IFN-alpha treatment as did the KYN/TRP ratio, reflecting IDO activity, and the KYN/KA ratio, reflecting the neurotoxic challenge. The TRP/CAA (competing amino acids) ratio, reflecting TRP availability to the brain, did not significantly change during treatment. Total MADRS score was significantly associated over time with the KYN/KA ratio, but not with the TRP/CAA ratio. Although no support was found that IDO decreases TRP availability to the brain, this study does support a role for IDO activity in the pathophysiology of IFN-alpha-induced depressive symptoms, through its induction of neurotoxic KYN metabolites.
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PMID:IDO and interferon-alpha-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity. 1549 6

After in vitro treatment of bacteriophage T4 with hydroxylamine (HA), 54 nonsense mutants in the rII A cistron were isolated. These mutants were characterized by growth on suppressor strains of Escherichia coli, and the mutational sites were mapped in the rII A cistron. Twenty-five (9 sites) were amber (UAG), 20 (6 sites) were opal (UGA), and 9 (6 sites) were ochre (UAA). Mapping experiments further indicated that there were three closely linked pairs of amber and opal mutations, conceivably involving mutations occurring in adjacent nucleotides. Based on the specificity of HA mutagenesis (GC --> AT), the amino acid codons in which the mutations occurred have been inferred. It is suggested that the three amber-opal pairs arose in tryptophan codons (UGG) and the six ochre mutants arose in glutamine codons (CAA). The six unpaired ambers and the three unpaired opals have been tentatively assigned to glutamine codons (CAG) and arginine codons (CGA), respectively, in the wild-type phage.
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PMID:Nonsense Mutants in the rII A Cistron of Bacteriophage T4. 1678 12

We isolated HIV-1 Envelope (Env)-specific memory B cells from a cow that had developed high titer polyclonal immunoglobulin G (IgG) with broad neutralizing activity after a long duration vaccination with HIV-1AD8 Env gp140 trimers. We cloned the bovine IgG matched heavy (H) and light (L) chain variable (V) genes from these memory B cells and constructed IgG monoclonal antibodies (mAbs) with either a human constant (C)-region/bovine V-region chimeric or fully bovine C and V regions. Among 42 selected Ig+ memory B cells, two mAbs (6A and 8C) showed high affinity binding to gp140 Env. Characterization of both the fully bovine and human chimeric isoforms of these two mAbs revealed them as highly type-specific and capable of binding only to soluble AD8 uncleaved gp140 trimers and covalently stabilized AD8 SOSIP gp140 cleaved trimers, but not monomeric gp120. Genomic sequence analysis of the V genes showed the third heavy complementarity-determining region (CDRH3) of 6A mAb was 21 amino acids in length while 8C CDRH3 was 14 amino acids long. The entire V heavy (VH) region was 27% and 25% diverged for 6A and 8C, respectively, from the best matched germline V genes available, and the CDRH3 regions of 6A and 8C were 47.62% and 78.57% somatically mutated, respectively, suggesting a high level of somatic hypermutation compared with CDRH3 of other species. Alanine mutagenesis of the VH genes of 6A and 8C, showed that CDRH3 cysteine and tryptophan amino acids were crucial for antigen binding. Therefore, these bovine vaccine-induced anti-HIV antibodies shared some of the notable structural features of elite human broadly neutralizing antibodies, such as CDRH3 size and somatic mutation during affinity-maturation. However, while the 6A and 8C mAbs inhibited soluble CD4 binding to gp140 Env, they did not recapitulate the neutralizing activity of the polyclonal antibodies against HIV infection.
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PMID:Trimeric gp120-specific bovine monoclonal antibodies require cysteine and aromatic residues in CDRH3 for high affinity binding to HIV Env. 2799 75


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