title: Nostosins, Trypsin Inhibitors Isolated from the Terrestrial Cyanobacterium Nostoc sp. Strain FSN.
abstract: Two new trypsin inhibitors, nostosin A (1) and B (2), were isolated from a hydrophilic extract of Nostoc sp. strain FSN, which was collected from a paddy field in the Golestan Province of Iran. Nostosins A (1) and B (2) are composed of three subunits, 2-hydroxy-4-(4-hydroxyphenyl)butanoic acid (Hhpba), L-Ile, and L-argininal (1) or argininol (2). Nostosins A (1) and B (2) exhibited IC50 values of 0.35 and 55 μM against porcine trypsin, respectively, suggesting that the argininal aldehyde group plays a crucial role in the efficient inhibition of trypsin. Molecular docking of nostosin A (1) (449 Da), leupeptin (426 Da, IC50 0.5 μM), and spumigin E (610 Da, IC50 < 0.1 μM) with trypsin suggested prominent binding similarity between nostosin A (1) and leupeptin but only partial binding similarity with spumigin E. The number of hydrogen bonds between ligands and trypsin increased according to the length and size of the ligand molecule, and the docking affinity values followed the measured IC50 values. Nostosin A (1) is the first highly potent three-subunit trypsin inhibitor with potency comparable to the known commercial trypsin inhibitor leupeptin. These findings expand the known diversity of short-chain linear peptide protease inhibitors produced by cyanobacteria.
authors: Division of Microbiology and Biotechnology, Department of Food and Environmental Sciences, University of Helsinki , P.O. Box 56, 00014, Helsinki, Finland.
authors: Liwei
authors: L
authors: Liu
authors: Division of Microbiology and Biotechnology, Department of Food and Environmental Sciences, University of Helsinki , P.O. Box 56, 00014, Helsinki, Finland.
authors: Jouni
authors: J
authors: Jokela
authors: Division of Microbiology and Biotechnology, Department of Food and Environmental Sciences, University of Helsinki , P.O. Box 56, 00014, Helsinki, Finland.
authors: Matti
authors: M
authors: Wahlsten
authors: Department of Biology, Faculty of Science, Tarbiat Moallem University , 49 Dr. Mofatteh Avenue, P.O. Box 158153587, 15614, Tehran, Iran.
authors: Bahareh
authors: B
authors: Nowruzi
authors: Program in Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki , P.O. Box 65, 00014, Helsinki, Finland.
authors: Perttu
authors: P
authors: Permi
authors: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki , P.O. Box 56, 00014, Helsinki, Finland.
authors: Yue Zhou
authors: YZ
authors: Zhang
authors: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki , P.O. Box 56, 00014, Helsinki, Finland.
authors: Henri
authors: H
authors: Xhaard
authors: Division of Microbiology and Biotechnology, Department of Food and Environmental Sciences, University of Helsinki , P.O. Box 56, 00014, Helsinki, Finland.
authors: David P
authors: DP
authors: Fewer
authors: Division of Microbiology and Biotechnology, Department of Food and Environmental Sciences, University of Helsinki , P.O. Box 56, 00014, Helsinki, Finland.
authors: Kaarina
authors: K
authors: Sivonen
mesh_terms: D020128:Inhibitory Concentration 50; D007492:Iran; D007976:Leupeptins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D046937:Nostoc / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014361:Trypsin Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D007976:Leupeptins; D009842:Oligopeptides; D014361:Trypsin Inhibitors; C000601918:nostosin A; C000601919:nostosin B; C032854:leupeptin