Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.69 (botulinum neurotoxin)
 1,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nuclear magnetic resonance (NMR) spectroscopy is a powerful technique for studying bimolecular interactions at the atomic scale. Our NMR laboratory is involved in the identification of small molecules, or ligands, that bind to target protein receptors such as tetanus neurotoxin (TeNT) and botulinum neurotoxin, anthrax proteins, and HLA-DR10 receptors on non-Hodgkin lymphoma cancer cells. Once low-affinity binders are identified, they can be linked together to produce multidentate synthetic high-affinity ligands (SHALs) that have very high specificity for their target protein receptors. An important nanotechnology application for SHALs is their use in the development of robust chemical sensors or biochips for the detection of pathogen proteins in environmental samples or body fluids. Here we describe a recently developed NMR competition assay based on transferred nuclear Overhauser effect spectroscopy that enables the identification of sets of ligands that bind to the same site, or a different site, on the surface of TeNT fragment C (TetC) than a known "marker" ligand, doxorubicin. Using this assay, one can identify the optimal pairs of ligands to be linked together for creating detection reagents, as well as estimate the relative binding constants for ligands competing for the same site.
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PMID:Application of NMR methods to identify detection reagents for use in development of robust nanosensors. 1565 83

A woman with Hashimoto's thyroiditis, under replacement L-T4, repeatedly experienced, over a 10-year period, elevations of serum TSH after eyelid injections of Clostridium botulinum neurotoxin A (Btx). We hypothesized a link between Btx injections and TSH elevations via molecular mimicry, and aimed to verify our hypothesis. Using an in silico approach, we searched first for amino acid sequence homology between Btx and thyroid autoantigens, and next for HLA binding motifs within homologous segments. We found that (i) Btx and thyroid autoantigens share amino acid sequence homology; (ii) some homologous regions contain epitopes of both Btx and thyroid autoantigens; (iii) some of such regions contain HLA-DR3 and/or HLA-DR7 binding motifs, which predominate over other HLA-DRs. This is relevant because the patient's HLA-DR haplotype was DR3/DR7. In conclusion, clinical and bioinformatics data suggest a possible pathogenetic link between Btx and autoimmune thyroid diseases. Considering the wide and increasing medical and dermocosmetic use of Btx, and the frequently subclinical course of autoimmune thyroid diseases, we think that thyroid "complications" may pass frequently undetected in Btx-treated persons.
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PMID:Injections of Clostridium botulinum neurotoxin A may cause thyroid complications in predisposed persons based on molecular mimicry with thyroid autoantigens. 2154 51

Previously, we have examined the proliferative responses of T-cells from 25 patients and 8 controls to 32 light chain (L1-L32) and 60 heavy chain peptides (N1-N29, C1-C31) representing the entire clostridium botulinum neurotoxin type A (BoNT/A)[OM1-OM3]. In the current work, these T-cell responses were analyzed in the context of the patients HLA-DRB1, DQA1 and DQB1 variation. There were strong associations between the DQA1*01:02 and its derived haplotypes and cumulative T-cell proliferative responses. With or without HLA based differentiation the responses showed marked correlation. Inter-epitope correlation of responses demonstrably associated with particular regions (peptides N1-N29) peaking in the region covered by of N18-29. A second region of higher correlation was observed close to the carboxyl terminal of the heavy chain. Region N15 to N29 was found to have a significantly lower Stimulation Indices when DRB1*01:01-DQA1*01:01-DQB1*05:01 was present. This pattern was also evident in the HLA analysis where DQA1*01:02 associations were collectively most significant in the N1-N13 & C16-C31 region. Responses in these regions correlated well with one another. HLA-specific correlation analysis revealed that DQA1*01:01 bearing haplotype had the strongest inter-epitope correlations despite having a generally negative association with simulation indices. Structural and immunogenic implications of these findings are discussed.
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PMID:Influences of HLA DRB1, DQA1 and DQB1 on T-cell recognition of epitopes and of larger regions of the botulinum neurotoxin molecule. 2882 19