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
References
Kurogi Y, Guner OF (2001) Curr Med Chem 8:1035–1055
Ekins S (2004) Drug Discovery Today 9:276–285
Jorgensen WL (2004) Science 303:1813–1818
Bajorath J (2002) Nat Rev Drug Discovery 1:882–894
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Adv Drug Delivery Rev 23:3–25
van de Waterbeemd H, Gifford E (2003) Nat Rev Drug Discovery 2:192–204
Lipinski CA (2004) Drug Discovery Today: Technologies 1:337–341
Shoichet BK (2004) Nature 432:862–865
Doman TN, McGovern SL, Witherbee BJ, Kasten TP, Kurumbail R, Stallings WC, Connolly DT, Shoichet BK (2002) J Med Chem 45:2213–2221
Funder JW (2005) Heart Fail Rev 10:15–22
Hu GX, Lian QQ, Lin H, Latif SA, Morris DJ, Hardy MP, Ge RS (2008) Steroids 73:1018–1024
Revollo JR, Cidlowski JA (2009) Ann NY Acad Sci 1179:167–178
Rabbitt EH, Lavery GG, Walker EA, Cooper MS, Stewart PM, Hewison M (2002) FASEB J 16:36–44
Kotelevtsev Y, Holmes MC, Burchell A, Houston PM, Schmoll D, Jamieson P, Best R, Brown R, Edwards CR, Seckl JR, Mullins JJ (1997) Proc Natl Acad Sci USA 94:14924–14929
Holmes MC, Kotelevtsev Y, Mullins JJ, Seckl JR (2001) Mol Cell Endocrinol 171:15–20
Morton NM, Holmes MC, Fievet C, Staels B, Tailleux A, Mullins JJ, Seckl JR (2001) J Biol Chem 276:41293–41300
Walker BR, Campbell JC, Williams BC, Edwards CR (1992) Endocrinology 131:970–972
Albiston AL, Obeyesekere VR, Smith RE, Krozowski ZS (1994) Mol Cell Endocrinol 105:R11–R17
Agarwal AK, Mune T, Monder C, White PC (1995) Endocr Res 21:389–397
Yamaguchi H, Kidachi Y, Kamiie K, Noshita T, Umetsu H, Ryoyama K (2010) Biol Pharm Bull 33:321–324
Carvajal CA, Gonzalez AA, Romero DG, González A, Mosso LM, Lagos ET, Hevia Mdel P, Rosati MP, Perez-Acle TO, Gomez-Sanchez CE, Montero JA, Fardella CE (2003) J Clin Endocrinol Metab 88:2501–2507
Koch MA, Wittenberg LO, Basu S, Jeyaraj DA, Gourzoulidou E, Reinecke K, Odermatt A, Waldmann H (2004) Proc Natl Acad Sci USA 101:16721–16726
Yamaguchi H, Akitaya T, Yu T, Kidachi Y, Kamiie K, Noshita T, Umetsu H, Ryoyama K (2011) Eur J Med Chem 46:1325–1330
Hosfield DJ, Wu Y, Skene RJ, Hilgers M, Jennings A, Snell GP, Aertgeerts K (2005) J Biol Chem 280:4639–4648
Ogg D, Elleby B, Norström C, Stefansson K, Abrahmsén L, Oppermann U, Svensson S (2005) J Biol Chem 280:3789–3794
Wan ZK, Chenail E, Xiang J, Li HQ, Ipek M, Bard J, Svenson K, Mansour TS, Xu X, Tian X, Suri V, Hahm S, Xing Y, Johnson CE, Li X, Qadri A, Panza D, Perreault M, Tobin JF, Saiah E (2009) J Med Chem 52:5449–5461
Ni XT, Duan T, Yang Z, Guo CM, Li JN, Sun K (2009) Placenta 30:1023–1028
Huang Y, Li X, Lin H, Chu Y, Chen B, Lian Q, Ge RS (2010) Biochem Biophys Res Commun 391:1752–1756
Levitt M (1992) J Mol Biol 226:507–533
Fechteler T, Dengler U, Schomberg D (1995) J Mol Biol 253:114–131
Liang J, Edelsbrunner H, Fu P, Sudhakar PV, Subramaniam S (1998) Proteins 33:1–17
Liang J, Edelsbrunner H, Fu P, Sudhakar PV, Subramaniam S (1998) Proteins 33:18–29
Goto J, Kataoka R, Hirayama N (2004) J Med Chem 47:6804–6811
Chang DT, Oyang YJ, Lin JH (2005) Nucleic Acids Res 33(suppl 2):W233–W238
Metropolis N, Ulam S (1949) J Am Stat Assoc 44:335–341
Metropolis N, Rosenbluth AW, Rosenbluth MN, Teller AH (1953) J Chem Phys 21:1087–1092
Goto J, Kataoka R, Muta H, Hirayama N (2008) J Chem Inf Model 48:583–590
Halgren TA (1996) J Comput Chem 17:490–519
Obeid J, White PC (1992) Biochem Biophys Res Commun 188:222–227
Oppermann UC, Filling C, Berndt KD, Persson B, Benach J, Ladenstein R, Jornvall H (1997) Biochemistry 36:34–40
Filling C, Berndt KD, Benach J, Knapp S, Prozorovski T, Nordling E, Ladenstein R, Jornvall H, Oppermann UC (2002) J Biol Chem 277:25677–25684
Hoffmann F, Maser E (2007) Drug Metab Rev 39:87–144
Vincent SJF, Zwahlen C, Post CB, Burgner JW, Bodenhausen G (1997) Proc Natl Acad Sci USA 94:4383–4388
Atanasov AG, Tam S, Rochen JM, Baker ME, Odermatt A (2003) Biochem Biophys Res Commun 308:257–262
Schuster D, Maurer EM, Laggner C, Nashev LG, Wilckens T, Langer T, Odermatt A (2006) J Med Chem 49:3454–3466
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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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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