寄生在魚類和貝類里的單細胞藻類會產(chǎn)生毒素，人們?nèi)绻秤昧吮桓腥镜暮．a(chǎn)品,，就會出現(xiàn)腹瀉,、麻痹或是神經(jīng)方面的問題。法國國家科研中心3月10日報告說,，法美兩國科學家最近發(fā)現(xiàn)了兩種海鮮毒素的致病機制,。
來自法國國家科研中心、法國原子能委員會和美國加利福尼亞大學的研究人員在新一期美國《美國科學院院刊》（PNAS）上介紹說,，他們選取兩種名為spirolide和gymnodimine的海鮮藻毒素為研究對象,，將這兩種毒素分別注入實驗鼠體內(nèi)，結(jié)果幾分鐘內(nèi),，實驗鼠就出現(xiàn)了嚴重的精神紊亂,。
研究人員分析發(fā)現(xiàn)，藻毒素的攻擊對象是一種位于肌肉和神經(jīng)細胞膜上的接收器,。這種名為nrACh的接收器一旦被藻毒素控制,，就會導(dǎo)致肌肉和大腦等運行異常。
研究人員說,，這一發(fā)現(xiàn)將有助于藻毒素解毒藥物的研發(fā),。自1991年以來，加拿大,、挪威,、西班牙,、突尼斯和法國等多個國家相繼發(fā)現(xiàn)了被藻毒素感染的海鮮。因此,，研發(fā)藻毒素解毒藥物無論在公共衛(wèi)生方面還是經(jīng)濟效益方面都至關(guān)重要,。(生物谷Bioon.com)
生物谷推薦原文出處：
PNAS doi: 10.1073/pnas.0912372107
Structural determinants in phycotoxins and AChBP conferring high affinity binding and nicotinic AChR antagonism
Yves Bournea,1, Zoran Radi?b, Rómulo Aráozc, Todd T. Talleyb, Evelyne Benoitc, Denis Serventd, Palmer Taylorb, Jordi Molgóc, and Pascale Marchote,1
Spirolide and gymnodimine macrocyclic imine phycotoxins belong to an emerging class of chemical agents associated with marine algal blooms and shellfish toxicity. Analysis of 13-desmethyl spirolide C and gymnodimine A by binding and voltage-clamp recordings on muscle-type α12βγδ and neuronal α3β2 and α4β2 nicotinic acetylcholine receptors reveals subnanomolar affinities, potent antagonism, and limited subtype selectivity. Their binding to acetylcholine-binding proteins (AChBP), as soluble receptor surrogates, exhibits picomolar affinities governed by diffusion-limited association and slow dissociation, accounting for apparent irreversibility. Crystal structures of the phycotoxins bound to Aplysia-AChBP (≈2.4?) show toxins neatly imbedded within the nest of ar-omatic side chains contributed by loops C and F on opposing faces of the subunit interface, and which in physiological conditions accommodates acetylcholine. The structures also point to three major features: (i) the sequence-conserved loop C envelops the bound toxins to maximize surface complementarity; (ii) hydrogen bonding of the protonated imine nitrogen in the toxins with the carbonyl oxygen of loop C Trp147 tethers the toxin core centered within the pocket; and (iii) the spirolide bis-spiroacetal or gymnodimine tetrahydrofuran and their common cyclohexene-butyrolactone further anchor the toxins in apical and membrane directions, along the subunit interface. In contrast, the se-quence-variable loop F only sparingly contributes contact points to preserve the broad receptor subtype recognition unique to phycotoxins compared with other nicotinic antagonists. These data offer unique means for detecting spiroimine toxins in shellfish and identify distinctive ligands, functional determinants and binding regions for the design of new drugs able to target several receptor subtypes with high affinity.
