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

Toxins

Andrea Figueroa-Montiel¹  Alexei Licea-Navarro¹  Johanna Bernáldez¹  Samanta Jiménez¹  Beatrix Ueberhide²  Luis Javier González³ 

[1] 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;Laboratorio de Espectrometría de Masas, Departamento de Proteómica, Centro de Ingeniería Genética y Biotecnología, Avenida 31 e/158 y 190, Cubanacán, Playa, P.O. Box 6162, C.P. 10600 La Habana, Cuba;

关键词: Conasprella ximenes;    mass spectrometry;    EThcD;    transcriptome;    conotoxins;    de novo sequencing;    antimycobacterial;    tuberculosis;   

DOI  :  10.3390/toxins10020051

来源: DOAJ

【 摘 要 】

Mycobacterium tuberculosis 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 M. tuberculosis 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 Conasprella ximenes. The venom gland transcriptome of C. ximenes 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.

【 授权许可】

Unknown