title: Molecular modeling of human acidic mammalian chitinase in complex with the natural-product cyclopentapeptide chitinase inhibitor argifin.
abstract: Human acidic mammalian chitinase (hAMCase) is an attractive target for developing anti-asthma medications. We used a variety of computational methods to investigate the interaction between hAMCase and the natural-product cyclopentapeptide chitinase inhibitor argifin. The three-dimensional structure of hAMCase was first constructed using homology modeling. The interaction mode and binding free energy between argifin and hAMCase were then examined by the molecular-docking calculation and the molecular mechanics Poisson-Boltzmann surface area method combined with molecular dynamics simulation, respectively. The results suggested that argifin binds to hAMCase in a similar fashion to the interaction mode observed in the crystal structure of argifin-human chitotriosidase complex, and possesses inhibitory activity against hAMCase in the micromolar range. We further designed argifin derivatives expected to be selective for hAMCase.
authors: School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. godah@pharm.kitasato-u.ac.jp
authors: Hiroaki
authors: H
authors: Gouda
authors: Shinichi
authors: S
authors: Terashima
authors: Kanami
authors: K
authors: Iguchi
authors: Akihiro
authors: A
authors: Sugawara
authors: Yoshifumi
authors: Y
authors: Saito
authors: Tsuyoshi
authors: T
authors: Yamamoto
authors: Tomoyasu
authors: T
authors: Hirose
authors: Kazuro
authors: K
authors: Shiomi
authors: Toshiaki
authors: T
authors: Sunazuka
authors: Satoshi
authors: S
authors: Omura
authors: Shuichi
authors: S
authors: Hirono
mesh_terms: D000595:Amino Acid Sequence; D018927:Anti-Asthmatic Agents / Q000737:chemistry* / Q000494:pharmacology; D002688:Chitinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003198:Computer Simulation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics
chemical_list: D018927:Anti-Asthmatic Agents; D004791:Enzyme Inhibitors; D010456:Peptides, Cyclic; C413566:argifin; D002688:Chitinases