Guddat L W, Martin J A, Shan L, Edmundson A B, Gray W R
Centre for Drug Design and Development, University of Queensland, St. Lucia, Australia.
Biochemistry. 1996 Sep 3;35(35):11329-35. doi: 10.1021/bi960820h.
Predatory marine snails of the genus Conus paralyze their fish prey by injecting a potent toxin. The alpha-conotoxin GI is a 13-residue peptide isolated from venom of Conus geographus. It functions by blocking the postsynaptic nicotinic acetylcholine receptor. After crystallization in deionized water, the three-dimensional structure of the GI neurotoxin was determined to 1.2 A resolution by X-ray crystallography. This structure, which can be described as a triangular slab, shows overall similarities to those derived by NMR, CD, and predictive methods. The principal framework of the molecule is provided by two disulfide bonds, one linking Cys 2 and Cys 7 and the other Cys 3 and Cys 13. Opposite ends of the sequence are drawn together even further by hydrogen bonds between Glu 1 and Cys 13 and between Cys 2 and Ser 12. Since the C-terminus is amidated, only one negative charge is present (carboxylate of Glu 1), and this is not implicated in receptor binding. Two positively charged regions (the alpha-amino group of Glu 1 and the guanido group of Arg 9) are situated 15 A apart at the corners of the triangular face of the molecule. phi, psi angles characteristic of a 3(10) helix were observed for residues 5-7. For residues 8-11, these angles were consistent with either a type I beta-turn or a distorted 3(10) helix.
芋螺属的掠食性海蜗牛通过注射一种强效毒素使鱼类猎物麻痹。α-芋螺毒素GI是一种从地纹芋螺毒液中分离出的由13个氨基酸残基组成的肽。它通过阻断突触后烟碱型乙酰胆碱受体发挥作用。在去离子水中结晶后，通过X射线晶体学确定了GI神经毒素的三维结构，分辨率为1.2埃。该结构可描述为一个三角形平板，与通过核磁共振、圆二色光谱和预测方法得到的结构总体相似。分子的主要框架由两个二硫键提供，一个连接半胱氨酸2和半胱氨酸7，另一个连接半胱氨酸3和半胱氨酸13。序列的相对两端通过谷氨酸1与半胱氨酸13之间以及半胱氨酸2与丝氨酸12之间的氢键进一步拉近。由于C末端被酰胺化，所以只存在一个负电荷（谷氨酸1的羧酸盐），且该电荷与受体结合无关。两个带正电荷的区域（谷氨酸1的α-氨基和精氨酸9的胍基）位于分子三角形面的角上，相距15埃。观察到第5至7位残基具有3(10)螺旋特征的φ、ψ角。对于第8至11位残基，这些角度与I型β-转角或扭曲的3(10)螺旋一致。
