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)

A scheme based on the zinc binding site [1992, FEBS Lett. 312, 110-114] has been extended to classify zinc metalloproteases into distinct families. The gluzincins, defined by the HEXXH motif and a glutamic acid as the third zinc ligand, include the thermolysin, endopeptidase-24.11, aminopeptidase, angiotensin converting enzyme, endopeptidase-24.15, and tetanus and botulinum neurotoxin families. The metzincins, defined by the HEXXH motif, a histidine as the third zinc ligand and a Met-turn, include the astacin, serralysin, reprolysin and matrixin families. The inverted zincin motif, HXXEH, defines the inverzincin family of insulin-degrading enzymes, the HXXE motif defines the carboxypeptidase family, and the HXH motif DD-carboxypeptidase.
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PMID:Families of zinc metalloproteases. 795 88

Clostridium botulinum type B neurotoxin was effectively bound to synaptotagmin 2 (Stg2) associated with ganglioside GT1b, however, the molecular interaction between the neurotoxin and the Stg2/GT1b complex has not been identified. Previously, we found that infant botulism-related strain 111 generated a low activity of the neurotoxin (111/NT), which differed in some amino acid residues, especially in the carboxyl terminal half of the heavy chain (H(C)), from the original neurotoxin of strain Okra (Okra/NT) associated with a food-borne botulism. In this study, we evaluated the binding capabilities of site-directed mutants of Okra/H(C) to the Stg2/GT1b complex and to GT1b alone, and investigated the relationship between the toxic action and receptor binding. Replacement of K1187 and E1190 with glutamic acid and lysine, respectively, which substituted for the 111/NT residues, caused a reduction of binding affinity to the Stg2/GT1b complex, suggesting that both these residues contribute to the different binding affinity between Okra/NT and 111/NT. Substitution of four residues, H1240, S1259, W1261 and Y1262, which form a ganglioside pocket, drastically decreased the binding of H(C) to the Stg2/GT1b complex and to GT1b. Mutation in the residues, K1186, E1189, K1191 and K1260 reduced the binding of H(C) to GT1b alone, but not to the Stg2/GT1b complex. Analyses of effects of mutant toxins on toxicity of BoNT/B to cerebellar granule cells suggest the association of cell toxicity with binding to Stg2/GT1b complex but not that to GT1b alone.
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PMID:Differential contribution of the residues in C-terminal half of the heavy chain of botulinum neurotoxin type B to its binding to the ganglioside GT1b and the synaptotagmin 2/GT1b complex. 1718 34

The afferent innervation of the urinary bladder consists primarily of small myelinated (Adelta) and unmyelinated (C-fiber) axons that respond to chemical and mechanical stimuli. Immunochemical studies indicate that bladder afferent neurons synthesize several putative neurotransmitters, including neuropeptides, glutamic acid, aspartic acid, and nitric oxide. The afferent neurons also express various types of receptors and ion channels, including transient receptor potential channels, purinergic, muscarinic, endothelin, neurotrophic factor, and estrogen receptors. Patch-clamp recordings in dissociated bladder afferent neurons and recordings of bladder afferent nerve activity have revealed that activation of many of these receptors enhances neuronal excitability. Afferent nerves can respond to chemicals present in urine as well as chemicals released in the bladder wall from nerves, smooth muscle, inflammatory cells, and epithelial cells lining the bladder lumen. Pathological conditions alter the chemical and electrical properties of bladder afferent pathways, leading to urinary urgency, increased voiding frequency, nocturia, urinary incontinence, and pain. Neurotrophic factors have been implicated in the pathophysiological mechanisms underlying the sensitization of bladder afferent nerves. Neurotoxins such as capsaicin, resiniferatoxin, and botulinum neurotoxin that target sensory nerves are useful in treating disorders of the lower urinary tract.
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PMID:Afferent nerve regulation of bladder function in health and disease. 1965 6