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抗分枝杆菌活性:在首次报道的西门氏锥蝽毒素中发现的 Conotoxin 的新药理靶点。

Antimycobacterial Activity: A New Pharmacological Target for Conotoxins Found in the First Reported Conotoxin from Conasprella ximenes.

机构信息

Departamento de Innovación Biomédica, CICESE, Carretera Ensenada-Tijuana 3918, Ensenada, BC C.P. 22860, Mexico.

Department of Biochemistry and Molecular Pharmacology, New York University, Langone Medical Center. 430 East, 29th Street, New York, NY 10016, USA.

出版信息

Toxins (Basel). 2018 Jan 23;10(2):51. doi: 10.3390/toxins10020051.

Abstract

is the etiological agent of tuberculosis, an airborne infectious disease that is a leading cause of human morbidity and mortality worldwide. We report here the first conotoxin that is able to inhibit the growth of at a concentration similar to that of two other drugs that are currently used in clinics. Furthermore, it is also the first conopeptide that has been isolated from the venom of The venom gland transcriptome of was sequenced to construct a database with 24,284 non-redundant transcripts. The conopeptide was purified from the venom using reverse phase high performance liquid chromatography (RP-HPLC) and was analyzed using electrospray ionization-mass spectrometry (ESI-MS/MS). No automatic identification above the identity threshold with 1% of the false discovery rate was obtained; however, a 10-amino-acid sequence tag, manually extracted from the MS/MS spectra, allowed for the identification of a conotoxin in the transcriptome database. Electron transfer higher energy collision dissociation (EThcD) fragmentation of the native conotoxin confirmed the N-terminal sequence (1-14), while LC-MS/MS analysis of the tryptic digest of the reduced and S-alkylated conotoxin confirmed the C-terminal region (15-36). The expected and experimental molecular masses corresponded, within sub-ppm mass error. The 37-mer peptide (MW 4109.69 Da), containing eight cysteine residues, was named I1_xm11a, according to the current nomenclature for this type of molecule.

摘要

结核分枝杆菌是结核病的病原体,这是一种空气传播的传染病,是全球人类发病率和死亡率的主要原因。我们在这里报告了第一个能够抑制 生长的芋螺毒素,其浓度与目前临床使用的两种药物相似。此外,它也是第一个从 毒液中分离出来的 conopeptide。对 的毒液腺转录组进行了测序,构建了一个包含 24284 个非冗余转录本的数据库。使用反相高效液相色谱 (RP-HPLC) 从毒液中纯化 conopeptide,并使用电喷雾电离-质谱 (ESI-MS/MS) 进行分析。在 1%假发现率的身份阈值以上没有获得自动识别;然而,从 MS/MS 光谱手动提取的 10 个氨基酸序列标签允许在转录组数据库中鉴定出一种芋螺毒素。天然芋螺毒素的电子转移高能碰撞解离 (EThcD) 碎裂证实了 N 端序列 (1-14),而还原和 S-烷基化芋螺毒素的胰蛋白酶消化产物的 LC-MS/MS 分析证实了 C 端区域 (15-36)。预期和实验分子量在亚 ppm 质量误差范围内相对应。该 37 肽 (MW 4109.69 Da),含有 8 个半胱氨酸残基,根据此类分子的当前命名法,命名为 I1_xm11a。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c9/5848152/088953d7b9ad/toxins-10-00051-g001.jpg

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