A novel post translational modification involving bromination of tryptophan - Identification of the residue, L-6-bromotryptophan, in peptides from Conus imperialis and Conus radiatus venom
A novel post translational modification involving bromination of tryptophan - Identification of the residue, L-6-bromotryptophan, in peptides from Conus imperialis and Conus radiatus venom
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DOI：
10.1074/jbc.272.8.4689
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发表时间：
1997-02-21
影响因子：
4.8
通讯作者：
McIntosh, JM
中科院分区：
文献类型：
--
作者：
Craig, AG;Jimenez, EC;McIntosh, JM
我们报告了一种新的翻译后修饰，涉及卤化色氨酸的肽回收的毒液的食肉海洋锥螺（芋螺）。在一个从帝王芋螺（Conusimperialis）中分离的七肽序列中鉴定出残基L-6-溴色氨酸，该肽在小鼠中枢或外周注射时不引起明显的行为症状，在来自辐射芋螺（Conusradiatus）的一个33-氨基酸肽中也鉴定出L-6-溴色氨酸;该肽已显示在所有年龄的小鼠中诱导睡眠样状态，并被称为溴睡眠肽。使用质谱法的组合测定两种肽Pca-Cys-Gly-Gln-Ala-Trp*-Cys-NH 2 [GRAPHICS]的序列，氨基酸和化学序列分析，其中Pca =焦谷氨酸，Hyp =羟脯氨酸，Gla = γ-羧基谷氨酸，Trp* = L-6-溴色氨酸。通过合成、共洗脱和酶水解实验确定修饰残基的精确结构和立体化学为L-6-溴色氨酸，据我们所知，这是在真核系统中修饰肽/蛋白质中色氨酸残基的第一个文件，也是色氨酸在体内卤化的第一个报告。
We report a novel post-translational modification involving halogenation of tryptophan in peptides recovered from the venom of carnivorous marine cone snails (Conus). The residue, L-6-bromotryptophan, was identified in the sequence of a heptapeptide, isolated from Conus imperialis, a worm-hunting cone, This peptide does not elicit gross behavioral symptoms when injected centrally or peripherally in mice, L-6-Bromotryptophan was also identified in a 33-amino acid peptide from Conus radiatus; this peptide has been shown to induce a sleep-like state in mice of all ages and is referred to as bromosleeper peptide, The sequences of the two peptidesPca-Cys-Gly-Gln-Ala-Trp*-Cys-NH2[GRAPHICS]were determined using a combination of mass spectrometry, amino acid, and chemical sequence analyses, where Pca = pyroglutamic acid, Hyp = hydroxyproline, Gla = gamma-carboxyglutamate, and Trp* = L-6-bromotryptophan, The precise structure and stereo chemistry of the modified residue were determined as L-6-bromotryptophan by synthesis, co elution, and enzymatic hydrolysis experiments, To our knowledge this is the first documentation of tryptophan residues in peptides/proteins being modified in a eukaryotic system and the first report of halogenation of tryptophan in vivo.