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

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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+.

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Abbreviations

11βHSD:

11β-hydroxysteroid dehydrogenase

ASE-dock:

Alpha sphere and excluded volume-based ligand-protein docking

HTS:

High throughput screening

LBS:

Ligand-binding site

MOE:

Molecular operating environment

MOE-dock:

Molecular operating environment docking

VS:

Virtual screening

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Acknowledgments

This study was partially supported by a grant-in-aid from the Promotion and Mutual Aid Corporation for Private Schools of Japan.

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Authors and Affiliations

  1. Department of Pharmacy, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku, Nagoya, 468–8503, Japan

    Hideaki Yamaguchi & Tatsuo Akitaya

  2. Graduate School of Medicine, Department of Functional Diagnostic Science, Osaka University, 1-7 Yamadaoka, Suita, Osaka, 565–0871, Japan

    Tao Yu

  3. Department of Pharmacy, Faculty of Pharmaceutical Sciences, Aomori University, 2-3-1 Kobata, Aomori, 030–0943, Japan

    Yumi Kidachi, Katsuyoshi Kamiie & Kazuo Ryoyama

  4. Department of Life Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka, Shobara, 727–0023, Japan

    Toshiro Noshita

  5. Laboratory of Food Chemistry, Department of Life Sciences, Junior College, Gifu Shotoku Gakuen University, 1-38 Nakauzura, Gifu, 055–8288, Japan

    Hironori Umetsu

Authors
  1. Hideaki Yamaguchi
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  2. Tatsuo Akitaya
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  3. Tao Yu
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  4. Yumi Kidachi
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  5. Katsuyoshi Kamiie
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  6. Toshiro Noshita
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  7. Hironori Umetsu
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  8. Kazuo Ryoyama
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Correspondence to Hideaki Yamaguchi.

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Yamaguchi, H., Akitaya, T., Yu, T. et al. Molecular docking and structural analysis of cofactor-protein interaction between NAD+ and 11β-hydroxysteroid dehydrogenase type 2. J Mol Model 18, 1037–1048 (2012). https://doi.org/10.1007/s00894-011-1140-2

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  • DOI: https://doi.org/10.1007/s00894-011-1140-2

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