• Rational discovery of testoste...

*Result*: Rational discovery of testosterone-enhancing peptide (AGNYGLPT) from sea cucumber: targeting T-type calcium channels through docking, molecular dynamics simulations, and cellular validation.

Title:
Rational discovery of testosterone-enhancing peptide (AGNYGLPT) from sea cucumber: targeting T-type calcium channels through docking, molecular dynamics simulations, and cellular validation.
Authors:
Luo X; Engineering Research Center of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou, Fujian 350002, China; College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China. Electronic address: lxlsky008@163.com., Liu T; Engineering Research Center of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou, Fujian 350002, China; College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China., Xu L; Engineering Research Center of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou, Fujian 350002, China; College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China., Guan Q; Engineering Research Center of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou, Fujian 350002, China; College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China., Zheng B; Engineering Research Center of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou, Fujian 350002, China; College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China., Zheng Y; Engineering Research Center of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou, Fujian 350002, China; College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China., Liu W; Food Nutrition and Health Research Center, Fuzhou University, Fuzhou, Fujian 350108, China. Electronic address: liuwangxin24@163.com.
Source:
Food research international (Ottawa, Ont.) [Food Res Int] 2026 Feb 01; Vol. 225, pp. 118078. Date of Electronic Publication: 2025 Dec 15.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Published on behalf of the Canadian Institute of Food Science and Technology by Elsevier Applied Science Country of Publication: Canada NLM ID: 9210143 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-7145 (Electronic) Linking ISSN: 09639969 NLM ISO Abbreviation: Food Res Int Subsets: MEDLINE
Imprint Name(s):
Original Publication: Ottawa, Ontario, Canada : Published on behalf of the Canadian Institute of Food Science and Technology by Elsevier Applied Science, c1992-
MeSH Terms:
Testosterone*/biosynthesis , Testosterone*/metabolism , Calcium Channels, T-Type*/metabolism , Calcium Channels, T-Type*/drug effects , Peptides*/pharmacology , Peptides*/chemistry , Sea Cucumbers*/chemistry , Molecular Docking Simulation*, Calcium/metabolism ; Animals ; Molecular Dynamics Simulation ; Humans
Contributed Indexing:
Keywords: Molecular docking; Molecular dynamics simulation; Sea cucumber peptides; T-type calcium channel; Testosterone
Substance Nomenclature:
3XMK78S47O (Testosterone)
0 (Calcium Channels, T-Type)
0 (Peptides)
SY7Q814VUP (Calcium)
Entry Date(s):
Date Created: 20260109 Date Completed: 20260109 Latest Revision: 20260109
Update Code:
20260130
DOI:
10.1016/j.foodres.2025.118078
PMID:
41508497
Database:
MEDLINE

*Further Information*

*Calcium ions (Ca<sup>2+</sup>) are a crucial signaling factor in testosterone synthesis. This study employed computer-guided peptide screening and mechanism exploration to elucidate how sea cucumber peptide (SCP) promotes testosterone synthesis via Cacna1g (T-type calcium channel). Ca<sup>2+</sup> treatment alone significantly upregulated the expression of Cacna1g, protein kinase C (PKC), protein kinase A (PKA), and testosterone synthase genes (StAR, Hsd17b3, Cyp17a1); these effects were further enhanced by SCP co-treatment. Molecular docking combined with correlation analysis pinpointed the peptide's isoelectric point as a critical determinant governing its binding affinity to Cacna1g. SCP was subsequently fractionated into three components via ion-exchange chromatography, among which the fraction 1 (F1) elevated intracellular Ca<sup>2+</sup> levels and enhanced testosterone synthesis. Moreover, molecular docking results for the F1 sequences also showed a positive linear relationship between binding affinity and isoelectric point. Peptide AGNYGLPT in F1 stabilizes Cacna1g (with the strongest binding ability) via hydrogen bonding, and participates in ion channel formation (Charge = -2, Radius = 2.8 Å). In vitro, AGNYGLPT increased intracellular Ca<sup>2+</sup> levels and enhanced testosterone synthesis, but this effect was abolished by inhibition of T-type calcium channels. This study provided mechanistic insights into peptide-channel interactions and offered new ideas for computer-assisted screening of active peptides.
(Copyright © 2024. Published by Elsevier Ltd.)*

*Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.*