9XE5
Defensin-like inhibitor of mammalian amylases, magnificamide-2, from the sea anemone Heteractis magnifica
Summary for 9XE5
| Entry DOI | 10.2210/pdb9xe5/pdb |
| Descriptor | Alpha-amylase inhibitor magnificamide (1 entity in total) |
| Functional Keywords | hydrolase inhibitor, beta-defensin, mammalian alpha-amylase inhibitor, toxin |
| Biological source | Heteractis magnifica (magnificent sea anemone) |
| Total number of polymer chains | 1 |
| Total formula weight | 4790.50 |
| Authors | Menshov, A.,Paramonov, A.,Popkova, D.,Shenkarev, Z.,Leychenko, E. (deposition date: 2025-10-27, release date: 2026-10-28) |
| Primary citation | Popkova, D.,Menshov, A.,Sintsova, O.,Paramonov, A.,Kalina, R.,Panina, I.,Kalinovskii, A.,Osmakov, D.,Shamatova, M.,Dmitrenok, P.,Chugunov, A.,Kozlov, S.,Efremov, R.,Shenkarev, Z.,Gladkikh, I.,Leychenko, E. Novel beta-defensin-like marine miniprotein magnificamide-2 with a remarkable potency in inhibiting mammalian alpha-amylases. Int.J.Biol.Macromol., 376:153418-153418, 2026 Cited by PubMed Abstract: Reducing polysaccharide degradation through inhibition of α-amylases and α-glucosidases is one of the strategies for glycemic control in the treatment of diabetes mellitus. Here we report the identification and characterization of a new β-defensin-like miniprotein magnificamide-2 (Mgf-2), one of the most potent inhibitors of mammalian α-amylases with subnanomolar binding affinity (K of recombinant Mgf-2 is 0.029 nM against human pancreatic α-amylase, 0.057 nM against human salivary α-amylase, and 0.011 nM against porcine pancreatic α-amylase). Using nuclear magnetic resonance (NMR) spectroscopy, ensemble protein-protein docking, and molecular dynamics (MD) simulations, the key structural determinants responsible for this ultra-tight inhibition were identified, which was subsequently confirmed by site-directed mutagenesis experiments. The β1-β2 loop containing the inhibitory motif YIYH plays a crucial role in the inhibitor-enzyme interaction by forming an extensive hydrophobic interface with the hydrophobic "rim" around the α-amylase active site. The data obtained enhance our understanding of the molecular mechanisms underlying high-affinity α-amylase inhibition and provide valuable insights into the design of novel proteinaceous α-amylase inhibitors for the treatment and prevention of postprandial hyperglycemia. PubMed: 42419540DOI: 10.1016/j.ijbiomac.2026.153418 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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