Three-dimensional structure of the mini-M conotoxin mr3a.

Three-dimensional structure of the mini-M conotoxin mr3a.
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mini-M 芋螺毒素 mr3a 的三维结构。

DOI:
10.1021/bi0353732
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发表时间:
2004
期刊:
影响因子:
2.9
通讯作者:
Poulter,CDale
Poulter,CDale
中科院分区:
生物学3区
文献类型:
--
作者:
McDougal,OwenM;Poulter,CDale

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来自真姬菇(Conus marmoreus)毒液的芋螺毒素mr 3a是一种诱导小鼠滚动癫痫发作的新型肽,其肽序列为GCCGSFACRFGCVOCCV,其中O是反式-4-羟脯氨酸,并且该链通过Cys-2和Cys-16、Cys-3和Cys-12以及Cys-8和Cys-15之间的二硫键交联。通过2D 1H NMR结合标准距离几何算法确定mr 3a的三级结构。基于51个NOE、6个氢键、6个二面角和3个二硫键约束,肽的最终一组22个结构的平均全局骨架RMS偏差为0.53 ± 0.22 μ m。芋螺毒素mr 3a是M超家族中芋螺肽新的mini-M分支的第一个例子。其结构已知的maxi-M分支的成员包括μ-芋螺毒素和β-芋螺毒素,两者共享共同的二硫键连接。虽然mr 3a具有与μ-和β-芋螺毒素相同的Cys残基排列,但其二硫键连接性不同。这给了mr 3a一个独特的“三圈”骨架。
Conotoxin mr3a from the venom ofConus marmoreus, a novel peptide that induces rolling seizures in mice, has the peptide sequence GCCGSFACRFGCVOCCV, where O istrans-4-hydroxyproline, and the chain is cross-linked with disulfide bonds between Cys-2 and Cys-16, Cys-3 and Cys-12, and Cys-8 and Cys-15. The tertiary structure of mr3a was determined by 2D1H NMR in combination with a standard distance−geometry algorithm. The final set of 22 structures for the peptide had a mean global backbone RMS deviation of 0.53 ± 0.22 Å based on 51 NOE, 6 hydrogen bond, 6 ϕ dihedral angle, and 3 disulfide bond constraints. Conotoxin mr3a is the first example of the new mini-M branch of conopeptides in the M superfamily. Members of the maxi-M branch, whose structures are known, include the μ- and ψ-conotoxins, both of which share a common disulfide bond connectivity. Although mr3a has the same arrangement of Cys residues as the μ- and ψ-conotoxins, its disulfide connectivity is different. This gives mr3a a distinctive “triple-turn” backbone.