Raymond S. Norton

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Throughout evolution, numerous proteins have been convergently recruited into the venoms of various animals, including centipedes, cephalopods, cone snails, fish, insects (several independent venom systems), platypus, scorpions, shrews, spiders, toxicoferan reptiles (lizards and snakes), and sea anemones. The protein scaffolds utilized convergently have(More)
Amyloid beta peptide (Abeta) is the major constituent of extracellular plaques and perivascular amyloid deposits, the pathognomonic neuropathological lesions of Alzheimer's disease. Cu(2+) and Zn(2+) bind Abeta, inducing aggregation and giving rise to reactive oxygen species. These reactions may play a deleterious role in the disease state, because high(More)
Viscera (48.3 kg) from moray eels (Lycodontis javanicus) collected in a ciguatera endemic area were extracted and the ciguatoxins characterized. Three major ciguatoxins, CTX-1, CTX-2 and CTX-3, were isolated and purified to homogeneity on reverse phase high performance liquid chromatography. Several minor toxins were also detected. CTX-1 (490 micrograms)(More)
Sea anemones produce a series of toxic polypeptides and proteins with molecular weights in the range 3000-5000 that act by binding to specific receptor sites on the voltage-gated sodium channel of excitable tissue. This article reviews our current knowledge of the molecular basis for activity of these molecules, with particular emphasis on recent results on(More)
The voltage-gated potassium channel in T lymphocytes, Kv1.3, is an important molecular target for immunosuppressive agents. A structurally defined polypeptide, ShK, from the sea anemone Stichodactyla helianthus inhibited Kv1.3 potently and also blocked Kv1.1, Kv1.4, and Kv1.6 at subnanomolar concentrations. Using mutant cycle analysis in conjunction with(More)
An increasing number of ion channel toxins and related polypeptides have been found to adopt a common structural motif designated the inhibitor cystine knot motif (Pallaghy P. K., Nielsen, K. J., Craik, D. J., Norton, R. S. (1994) A common structural motif incorporating a cystine knot and triple-stranded beta-sheet in toxic and inhibitory polypeptides.(More)
Insulin-like growth factor binding proteins (IGFBP-1 to -6) bind insulin-like growth factors-I and -II (IGF-I and IGF-II) with high affinity. These binding proteins maintain IGFs in the circulation and direct them to target tissues, where they promote cell growth, proliferation, differentiation, and survival via the type 1 IGF receptor. IGFBPs also interact(More)
Kv1.3 potassium channels maintain the membrane potential of effector memory (T(EM)) T cells that are important mediators of multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. The polypeptide ShK-170 (ShK-L5), containing an N-terminal phosphotyrosine extension of the Stichodactyla helianthus ShK toxin, is a potent and selective blocker(More)
The SOCS (suppressors of cytokine signalling) family of proteins inhibits the cytokine-induced signalling cascade in part by promoting the ubiquitination of signalling intermediates that are then targeted for proteasomal degradation. This activity relies upon an interaction between the SOCS box domain, the adapter complex elonginBC and a member of the(More)
Peptide neurotoxins from cone snails continue to supply compounds with therapeutic potential. Although several analgesic conotoxins have already reached human clinical trials, a continuing need exists for the discovery and development of novel non-opioid analgesics, such as subtype-selective sodium channel blockers. Micro-conotoxin KIIIA is representative(More)