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⁺.