PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 12734383-2 2003 Recently, we replaced the lipoic acid moiety of PDC-E2 with a battery of synthetic structures designed to mimic a xenobiotically modified lipoyl hapten on a 12-aa peptide that was found within the immunodominant autoepitope of PDC-E2 and demonstrated that AMA in PBC reacted against several organic modified mimotopes as well as, or sometimes significantly better than, the native lipoyl domain. Thioctic Acid 26-37 dihydrolipoamide S-acetyltransferase Homo sapiens 48-54 15558739-5 2004 The only purported regulatory system that prevents the accumulation of potentially autoreactive PDC-E2 is glutathionylation, in which the lysine-lipoic acid moiety is further modified with glutathione during apoptosis. Thioctic Acid 145-156 dihydrolipoamide S-acetyltransferase Homo sapiens 96-102 15554995-12 2004 Some of these xenobiotics are immunologically related to lipoic acid, the cofactor that is at the active center of PDC-E2. Thioctic Acid 57-68 dihydrolipoamide S-acetyltransferase Homo sapiens 115-121 9620315-3 1998 Immunodominant regions (autoepitopes) on the porcine-PDC-E2 component have been mapped to two regions around Lys-46 (outer lipoyl domain) and Lys-173 (inner lipoyl domain), which contained covalently bound lipoic acid prosthetic group. Thioctic Acid 206-217 dihydrolipoamide S-acetyltransferase Homo sapiens 53-59 11283841-2 2001 More than 95% of primary biliary cirrhosis (PBC) patients have detectable levels of autoantibodies to PDC-E2 and in general these react with a region of the molecule that contains the prosthetic group lipoic acid (LA). Thioctic Acid 201-212 dihydrolipoamide S-acetyltransferase Homo sapiens 102-108 7821922-3 1995 The epitope recognized by C355.1 is near the lipoic acid binding site of PDC-E2. Thioctic Acid 45-56 dihydrolipoamide S-acetyltransferase Homo sapiens 73-79 9089910-4 1997 The dominant B-cell autoepitope in PBC has been identified as the inner lipoic acid binding domain of PDC-E2, with the lipoic acid co-factor, which plays a critical role in E2 enzymatic activity, playing a role in autoantibody binding to antigen. Thioctic Acid 72-83 dihydrolipoamide S-acetyltransferase Homo sapiens 102-108 1701753-6 1990 Because lipoic acid is covalently bound to the zeta-amino group of the lysine residue of PDC-E2, the mutants were designed to replace the lysine residue in the lipoyl domain with glutamine, a negatively charged amino acid; histidine, a positively charged amino acid; and tyrosine, an aromatic amino acid. Thioctic Acid 8-19 dihydrolipoamide S-acetyltransferase Homo sapiens 89-95 2468528-2 1989 Limited tryptic digestion, which cleaves E2 into well-characterised domains, followed by Western blotting indicates that the main immunodominant region of PDC E2 lies within the lipoic acid-containing domains of the polypeptide. Thioctic Acid 178-189 dihydrolipoamide S-acetyltransferase Homo sapiens 155-161 3191998-4 1988 Thus, mammalian PDC-E2 differs as to the number of lipoic acid-binding sites from other dihydrolipoamide acyltransferases in both prokaryotic and eukaryotic organisms. Thioctic Acid 51-62 dihydrolipoamide S-acetyltransferase Homo sapiens 16-22 22920894-4 2012 Quantitative structure-activity relationship (QSAR) data indicates that acetaminophen metabolites are particularly immunoreactive with AMA, and we submit that in genetically susceptible hosts, electrophilic modification of lipoic acid in PDC-E2 by acetaminophen or similar drugs can facilitate a loss of tolerance and lead to the development of PBC. Thioctic Acid 223-234 dihydrolipoamide S-acetyltransferase Homo sapiens 238-244 28470667-9 2017 Importantly, cross-reactive mAbs also recognized lipoic acid, a mitochondrial fatty acid that is covalently bound to PDC-E2. Thioctic Acid 49-60 dihydrolipoamide S-acetyltransferase Homo sapiens 117-123 28100006-9 2017 We demonstrate that the conformation of PDC-E2 ILD is altered when conjugated with 2OA, compared to conjugation with lipoic acid. Thioctic Acid 117-128 dihydrolipoamide S-acetyltransferase Homo sapiens 40-46 23184636-10 2013 CONCLUSION: Specific modifications of the disulfide bond within the lipoic-acid-conjugated PDC-E2 moiety, i.e., by an electrophilic agent renders PDC-E2 immunogenic in a genetically susceptible host. Thioctic Acid 68-79 dihydrolipoamide S-acetyltransferase Homo sapiens 91-97 23184636-10 2013 CONCLUSION: Specific modifications of the disulfide bond within the lipoic-acid-conjugated PDC-E2 moiety, i.e., by an electrophilic agent renders PDC-E2 immunogenic in a genetically susceptible host. Thioctic Acid 68-79 dihydrolipoamide S-acetyltransferase Homo sapiens 146-152 23352659-3 2013 Immunologically, PBC is distinguished by immune mediated destruction of the intra hepatic bile ducts and the presence of high titer antimitochondrial autoantibodies (AMA) directed against a highly specific epitope within the lipoic acid binding domain of the pyruvate dehydrogenase E2 subunit (PDC-E2). Thioctic Acid 225-236 dihydrolipoamide S-acetyltransferase Homo sapiens 17-20 23352659-3 2013 Immunologically, PBC is distinguished by immune mediated destruction of the intra hepatic bile ducts and the presence of high titer antimitochondrial autoantibodies (AMA) directed against a highly specific epitope within the lipoic acid binding domain of the pyruvate dehydrogenase E2 subunit (PDC-E2). Thioctic Acid 225-236 dihydrolipoamide S-acetyltransferase Homo sapiens 294-300 23352659-9 2013 We submit that in genetically susceptible hosts, electrophilic modification of lipoic acid in PDC-E2 by acetaminophen or similar drugs can facilitate loss of tolerance and lead to the development of PBC. Thioctic Acid 79-90 dihydrolipoamide S-acetyltransferase Homo sapiens 94-100 23352659-9 2013 We submit that in genetically susceptible hosts, electrophilic modification of lipoic acid in PDC-E2 by acetaminophen or similar drugs can facilitate loss of tolerance and lead to the development of PBC. Thioctic Acid 79-90 dihydrolipoamide S-acetyltransferase Homo sapiens 199-202 19003917-1 2008 UNLABELLED: Lipoylated enzymes such as the E2 component of pyruvate dehydrogenase complex (PDC-E2) are targets for autoreactive immune responses in primary biliary cirrhosis, with lipoic acid itself forming a component of the dominant auto-epitopes. Thioctic Acid 180-191 dihydrolipoamide S-acetyltransferase Homo sapiens 91-97 21763105-5 2011 Our results demonstrate that AMA-positive PBC sera demonstrate marked reactivity against 6,8-bis(acetylthio)octanoic acid, implying that chemical modification of the lipoyl ring, i.e. disruption of the S-S disulfide, renders lipoic acid to its reduced form that will promote xenobiotic modification. Thioctic Acid 225-236 dihydrolipoamide S-acetyltransferase Homo sapiens 42-45 19003917-3 2008 Importantly, sensitization with proteins artificially substituted with the lipoic acid analogue xenobiotic 6-bromohexanoic acid (6BH) can induce an immune response that cross-reacts with PDC-E2. Thioctic Acid 75-86 dihydrolipoamide S-acetyltransferase Homo sapiens 187-193 19003917-5 2008 It was found that these enzymes could incorporate lipoic acid analogues including octanoic and hexanoic acids and the xenobiotic 6BH into PDC-E2. Thioctic Acid 50-61 dihydrolipoamide S-acetyltransferase Homo sapiens 138-144 19003917-7 2008 Importantly, competition studies showed that the relative incorporation of both 6BH and lipoic acid could be regulated by the balance between ATP and GTP, with the formation of 6BH-substituted PDC-E2 predominating in an ATP-rich environment. Thioctic Acid 88-99 dihydrolipoamide S-acetyltransferase Homo sapiens 193-199