Homology modeling and structural analysis of 11β-hydroxysteroid dehydrogenase type 2

Yamaguchi, Hideaki; Akitaya, Tatsuo; Tang, Yu; Kidachi, Yumi; Kamiie, Katsuyoshi; Noshita, Toshiro; Umetsu, Hironori; Ryoyama, Kazuo

doi:10.1016/j.ejmech.2011.01.054

Cited by 13 publications

(26 citation statements)

References 46 publications

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“…The secondary structure of the m11βHSD2 model exhibited a central 6-stranded all-parallel β-sheet sandwich-like structure, flanked on both sides by 3-helices (Fig. 1A and B), which are in agreement with the h11βHSD1 and 2 models 18,33. For the construction of the m11βHSD2 model, 10 independent models of the target proteins were built using a Boltzmann-weighted randomized modeling procedure in the MOE that is adapted from reports by Levitt21 and Fechteler et al22 The intermediate models were evaluated by a residue packing quality function, which is sensitive to the degrees to which non-polar side-chain groups are buried and hydrogen bonding opportunities are satisfied.…”

Section: Resultssupporting

confidence: 78%

“…The contact energy profiles of the homology-modeled m11βHSD2 (Fig. 3A) was compared with that of the X-ray structure of h11βHSD1 and the homology-modeled h11βHSD2,18 and the trends of the variation in the contact energy in most parts of the m11βHSD2 model were in good agreement with those of the h11βHSD1 and 2 structures. The binding site volume of the m11βHSD2 model was also calculated with the MOE.…”

Section: Resultssupporting

confidence: 53%

“…4A) to the reported LBS in h11βHSD2,16,18 and the ASE-Dock was performed to evaluate the present docking simulation. The simulation showed that the ligand (corticosterone) successfully bound to the LBS in m11βHSD2 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Homology modeling of m11βHSD2 was achieved by the same methods used for modeling h11βHSD2 in our previous study 18. In brief, the m11βHSD2 (NCBI reference sequence: NM_008289.2)19 sequence and the crystal structure coordinates of h11βHSD1 (PDB code: 3HFG)20 were loaded into the MOE.…”

Section: Methodsmentioning

confidence: 99%

“…Structure assessment was performed by the same methods described in our previous study 18. In brief, the overall geometric and stereochemical qualities of the final modeled structure of m11βHSD2 were examined using Ramachandran plots generated within the MOE 23,24.…”

Section: Methodsmentioning

confidence: 99%

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Mouse 11β-Hydroxysteroid Dehydrogenase Type 2 for Human Application: Homology Modeling, Structural Analysis and Ligand-Receptor Interaction

et al. 2011

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Mouse (m) 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) was homology-modeled, and its structure and ligand-receptor interaction were analyzed. The modeled m11βHSD2 showed significant 3D similarities to the human (h) 11βHSD1 and 2 structures. The contact energy profiles of the m11βHSD2 model were in good agreement with those of the h11βHSD1 and 2 structures. The secondary structure of the m11βHSD2 model exhibited a central 6-stranded all-parallel β-sheet sandwich-like structure, flanked on both sides by 3-helices. Ramachandran plots revealed that only 1.1% of the amino acid residues were in the disfavored region for m11βHSD2. Further, the molecular surfaces and electrostatic analyses of the m11βHSD2 model at the ligand-binding site exhibited that the model was almost identical to the h11βHSD2 model. Furthermore, docking simulation and ligand-receptor interaction analyses revealed the similarity of the ligand-receptor bound conformation between the m11βHSD2 and h11βHSD2 models. These results indicate that the m11βHSD2 model was successfully evaluated and analyzed. To the best of our knowledge, this is the first report of a m11βHSD2 model with detailed analyses, and our data verify that the mouse model can be utilized for application to the human model to target 11βHSD2 for the development of anticancer drugs.

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Section: Resultssupporting

confidence: 78%

Section: Resultssupporting

confidence: 53%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Mouse 11β-Hydroxysteroid Dehydrogenase Type 2 for Human Application: Homology Modeling, Structural Analysis and Ligand-Receptor Interaction

et al. 2011

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Molecular docking and structural analysis of cofactor-protein interaction between NAD+ and 11β-hydroxysteroid dehydrogenase type 2

et al. 2011

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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(+).

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Environmental Pollutants and Hydroxysteroid Dehydrogenases

Guo

2014

Vitamins &Amp; Hormones

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Homology modeling and structural analysis of 11β-hydroxysteroid dehydrogenase type 2

Cited by 13 publications

References 46 publications

Mouse 11β-Hydroxysteroid Dehydrogenase Type 2 for Human Application: Homology Modeling, Structural Analysis and Ligand-Receptor Interaction

Mouse 11β-Hydroxysteroid Dehydrogenase Type 2 for Human Application: Homology Modeling, Structural Analysis and Ligand-Receptor Interaction

Molecular docking and structural analysis of cofactor-protein interaction between NAD+ and 11β-hydroxysteroid dehydrogenase type 2

Environmental Pollutants and Hydroxysteroid Dehydrogenases

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