title: Molecular docking and structural analysis of cofactor-protein interaction between NAD⁺ and 11β-hydroxysteroid dehydrogenase type 2.
abstract: Molecular docking and structural analysis of the cofactor-protein interaction between NAD(+) and human (h) or mouse (m) 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) were performed with the molecular operating environment (MOE). 11βHSD1 (PDB code: 3HFG) was selected as a template for the 3D structure modeling of 11βHSD2. The MOE docking (MOE-dock) and the alpha sphere and excluded volume-based ligand-protein docking (ASE-dock) showed that both NAD(+)-h11βHSD2 and NAD(+)-m11βHSD2 models have a similar binding orientation to the template cofactor-protein model. Our present study also revealed that Asp91, Phe94, Tyr232 and Thr267 could be of importance in the interaction between NAD(+) and 11βHSD2. NADP(+) was incapable of entering into the cofactor-binding site of the 11βHSD2 models. The present study proposes the latest models for 11βHSD2 and its cofactor NAD(+), and to the best of our knowledge, this is the first report of a m11βHSD2 model with NAD(+).
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku, Nagoya 468-8503, Japan. hyamagu@meijo-u.ac.jp
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Akitaya
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kidachi
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Kamiie
authors.forename: Toshiro
authors.initials: T
authors.lastname: Noshita
authors.forename: Hironori
authors.initials: H
authors.lastname: Umetsu
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ryoyama
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009243:NAD / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding
chemical_list: D009243:NAD; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2