{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T16:02:27Z","timestamp":1777046547369,"version":"3.51.4"},"reference-count":40,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Agricultural Science and Technology Innovation Program","award":["A2025008"],"award-info":[{"award-number":["A2025008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Natural food-derived proteins are increasingly explored as alternatives to synthetic inhibitors for managing Type 2 diabetes mellitus. Despite the recognized health-promoting properties of Morchella esculenta, the potential of its bioactive proteins to modulate glucose metabolism remains largely unexplored. This study systematically investigated the structural basis and hypoglycemic mechanisms of MEP5 (Morchella esculenta Protein 5), a fucose-specific lectin from M. esculenta, using an integrated in silico pipeline. MEP5 (33.12 kDa) adopts a stable \u03b2-sheet-rich conformation and harbors a conserved fucose-binding carbohydrate-recognition domain. Protein\u2013protein docking revealed that intact MEP5 binds directly to surface glycans of human \u03b1-glucosidase, generating steric hindrance that obstructs the catalytic pocket. Simulated gastrointestinal digestion yielded a highly bioavailable peptide profile. Following a rigorous multiparametric screening for toxicity, allergenicity, and water solubility, 11 short oligopeptides were identified as potent dipeptidyl peptidase-IV (DPP-IV) inhibitors. Molecular docking demonstrated that the top-ranked peptides, QPPR, DGTY, and DPDSH, occupy the S2 pocket of DPP-IV and form hydrogen bonds with catalytic triad residues (Ser630\/His740). These findings delineate a dual-stage hypoglycemic mechanism, pre-digestion enzymatic blockade and post-digestion incretin regulation, and support the potential of MEP5 as a multifunctional candidate for glucose homeostasis-oriented functional foods.<\/jats:p>","DOI":"10.3390\/foods15091493","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T14:28:23Z","timestamp":1777040903000},"page":"1493","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Silico Structural Characterization and Hypoglycemic Potential of a Novel Fucose-Specific Lectin (MEP5) from Morchella esculenta"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2490-8860","authenticated-orcid":false,"given":"Wanchao","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Edible Fungi, Shanghai Academy of Agricultural Sciences, National Engineering Research Center of Edible Fungi, Key Laboratory of Edible Fungi Resources and Utilization (South), Ministry of Agriculture and Rural Affairs, Shanghai 201403, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Edible Fungi, Shanghai Academy of Agricultural Sciences, National Engineering Research Center of Edible Fungi, Key Laboratory of Edible Fungi Resources and Utilization (South), Ministry of Agriculture and Rural Affairs, Shanghai 201403, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Edible Fungi, Shanghai Academy of Agricultural Sciences, National Engineering Research Center of Edible Fungi, Key Laboratory of Edible Fungi Resources and Utilization (South), Ministry of Agriculture and Rural Affairs, Shanghai 201403, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Edible Fungi, Shanghai Academy of Agricultural Sciences, National Engineering Research Center of Edible Fungi, Key Laboratory of Edible Fungi Resources and Utilization (South), Ministry of Agriculture and Rural Affairs, Shanghai 201403, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Edible Fungi, Shanghai Academy of Agricultural Sciences, National Engineering Research Center of Edible Fungi, Key Laboratory of Edible Fungi Resources and Utilization (South), Ministry of Agriculture and Rural Affairs, Shanghai 201403, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Edible Fungi, Shanghai Academy of Agricultural Sciences, National Engineering Research Center of Edible Fungi, Key Laboratory of Edible Fungi Resources and Utilization (South), Ministry of Agriculture and Rural Affairs, Shanghai 201403, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"124830","DOI":"10.1016\/j.carbpol.2025.124830","article-title":"Molecular mechanism and structure-activity relationships of natural source polysaccharides in intervening type 2 diabetes mellitus through antioxidant effects: A systematic review","volume":"377","author":"Yang","year":"2026","journal-title":"Carbohyd. 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