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Structural and functional alterations of myoglobin by glucose-protein interactions

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Abstract

The interaction of blood glucose with heme proteins plays a key role in inducing diabetes, a serious disease threatening human health. In this study, we investigated the non-covalent interaction between glucose and myoglobin (Mb), both theoretically and experimentally, using molecular dynamics (MD) simulation combined with spectroscopic studies. It revealed that glucoses can occupy the side pocket of Mb, and bind closely to one of the xenon cavities in Mb, by hydrogen bonding interactions with two propionate groups of heme as well as surrounding amino acids. These interactions alter the conformation of the heme active site slightly and lead to an enhanced peroxidase activity of Mb, as determined by kinetic studies. This study provides general information for glucose-heme proteins interactions, and also for blood glucose-protein interactions for patients with diabetes.

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References

  1. Shaw JE, Sicree RA, Zimmet PZ (2010) Duabetes Res Clin Pract 87:4–14

    Article  CAS  Google Scholar 

  2. Dalziel M, Crispin M, Scanlan CN, Zitzmann N, Dwek RA (2014) Science 343:1235681

    Article  Google Scholar 

  3. De Rosa MC, Sanna MT, Messana I, Castagnola M, Galtieri A, Tellone E, Scatena R, Botta B, Botta M, Giardina B (1998) Biophys Chem 72:323–325

    Article  Google Scholar 

  4. Cussimanio BL, Booth AA, Todd P, Hudson BG, Khalifah RG (2003) Biophys Chem 105:743–755

    Article  CAS  Google Scholar 

  5. Sen S, Bose T, Roy A, Chakraborti AS (2007) Mol Cell Biochem 301:251–257

    Article  CAS  Google Scholar 

  6. Roy A, Sil R, Chakraborti AS (2010) Mol Cell Biochem 338:105–114

    Article  CAS  Google Scholar 

  7. Bokiej M, Livermore AT, Harris AW, Onishi AC, Sandwick RK (2011) Biochem Biophys Res Commun 407:191–196

    Article  CAS  Google Scholar 

  8. Nowicka P, Santoro N, Liu H, Lartaud D, Shaw MM, Goldberg R, Guandalini C, Savoye M, Rose P, Caprio S (2011) Diabetes Care 34:1306–13011

    Article  CAS  Google Scholar 

  9. Ackers GK, Holt JM (2006) J Biol Chem 281:11441–11443

    Article  CAS  Google Scholar 

  10. Urayama P, Phillips GN Jr, Gruner SM (2002) Structure 10:51–60

    Article  CAS  Google Scholar 

  11. Sigman JA, Kwok BC, Lu Y (2000) J Am Chem Soc 122:8192–8196

    Article  CAS  Google Scholar 

  12. Sigman JA, Kim HK, Zhao X, Carey JR, Lu Y (2003) Proc Natl Acad Sci U S A 100:3629–3634

    Article  CAS  Google Scholar 

  13. Miner KD, Mukherjee A, Gao YG, Null EL, Petrik ID, Zhao X, Yeung N, Robinson H, Lu Y (2012) Angew Chem Int Ed 51:5589–5592

    Article  CAS  Google Scholar 

  14. Yeung N, Lin YW, Gao YG, Zhao X, Russell BS, Lei L, Miner KD, Robinson H, Lu Y (2009) Nature 462:1079–1082

    Article  CAS  Google Scholar 

  15. Lin YW, Yeung N, Gao YG, Miner KD, Tian S, Robinson H, Lu Y (2010) Proc Natl Acad Sci U S A 107:8581–8586

    Article  CAS  Google Scholar 

  16. Lin YW, Yeung N, Gao YG, Miner KD, Lei L, Robinson H, Lu Y (2010) J Am Chem Soc 132:9970–9972

    Article  CAS  Google Scholar 

  17. Lin YW (2011) Proteins 79:679–684

    Article  CAS  Google Scholar 

  18. Lin YW, Nie CM, Liao LF (2012) J Mol Model 18:4409–4415

    Article  CAS  Google Scholar 

  19. Cooper CE, Vollard NB, Choueiri T, Wilson MT (2002) Biochem Soc Trans 30:280–282

    Article  CAS  Google Scholar 

  20. Karplus M, McCammon JA (2002) Nat Struct Biol 9:646–652

    Article  CAS  Google Scholar 

  21. Daggett V (2006) Chem Rev 106:1898–1916

    Article  CAS  Google Scholar 

  22. Sotomayor M, Schulten K (2007) Science 316:1144–1148

    Article  CAS  Google Scholar 

  23. Kandt C, Monticelli L (2010) Mehtods Mol Biol 654:423–440

    CAS  Google Scholar 

  24. Humphrey W, Dalke A, Schulten K (1996) J Mol Graph 14:33–38

    Article  CAS  Google Scholar 

  25. Kalé L, Skeel R, Bhandarkar M, Brunner R, Gursoy A, Krawetz N, Phillips J, Shinozaki A, Varadarajan K, Schulten K (1999) J Comp Phys 151:283–312

    Article  Google Scholar 

  26. MacKerell AD Jr, Bashford D, Bellott M Jr, Dunbrack RL, Evanseck J, Field MJ, Fischer S, Gao J, Guo H, Ha S, Joseph D, Kuchnir L, Kuczera K, Lau FTK, Mattos C, Michnick S, Ngo T, Nguyen DT, Prodhom B, Reiher IWE, Roux B, Schlenkrich M, Smith J, Stote R, Straub J, Watanabe M, Wiorkiewicz-Kuczera J, Yin D, Karplus M (1998) J Phys Chem B 102:3586–3616

    Article  CAS  Google Scholar 

  27. Autenrieth F, Tajkhorshid E, Baudry J, Luthey-Schulten Z (2004) J Comput Chem 25:1613–1622

    Article  CAS  Google Scholar 

  28. Hatcher E, Guvench O, Mackerell AD Jr (2009) J Chem Theo Comp 5:1315–1327

    Article  CAS  Google Scholar 

  29. Lin YW, Wu YM, Liao LF (2012) J Mol Model 18:1591–1596

    Article  CAS  Google Scholar 

  30. Maragliano L, Cottone G, Ciccotti G, Vanden-Eijnden E (2010) J Am Chem Soc 231:1010–1017

    Article  Google Scholar 

  31. Tilton RF Jr, Kuntz ID Jr, Petsko GA (1984) Biochemistry 23:2849–2857

    Article  CAS  Google Scholar 

  32. Savino C, Miele AE, Draghi F, Johnson KA, Sciara G, Brunori M, Vallone B (2009) Biopolymers 91:1097–1107

    Article  CAS  Google Scholar 

  33. Matsuo T, Nagai H, Hisaeda Y (2006) Chem Commun 29:3131–3133

    Article  Google Scholar 

  34. Lin YW, Dong SS, Liu JH, Nie CM, Wen GB (2013) J Mol Catal B Enzym 91:25–31

    Article  CAS  Google Scholar 

  35. Berglund GI, Carlsson GH, Smith AT, Szöke H, Henriksen A, Hajdu J (2002) Nature 417:463–468

    Article  CAS  Google Scholar 

  36. Finzel BC, Poulos TL, Kraut J (1984) J Biol Chem 259:13027–13036

    CAS  Google Scholar 

  37. Matsui T, Ozaki S, Liong E, Phillips GN Jr, Watanabe Y (1999) J Biol Chem 274:2838–2844

    Article  CAS  Google Scholar 

  38. Nagao S, Osuka H, Yamada T, Uni T, Shomura Y, Imai K, Higuchi Y, Hirota S (2012) Dalton Trans 41:11378–11385

    Article  CAS  Google Scholar 

  39. Hendgen-Cotta UB, Merx MW, Shiva S, Schmitz J, Becher S, Klare JP, Steinhoff HJ, Goedecke A, Schrader J, Gladwin MT, Kelm M, Rassaf T (2008) Proc Natl Acad Sci U S A 105:10256–10261

    Article  CAS  Google Scholar 

  40. Bhattacherjee A, Chakraborti AS (2011) Intern J Biol Macromol 48:202–209

    Article  CAS  Google Scholar 

  41. Sun MH, Li W, Liu JH, Wen GB, Tan X, Lin YW (2013) RSC Adv 3:9337–9343

    Article  CAS  Google Scholar 

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Acknowledgments

It is a pleasure to acknowledge Professor S. G. Sligar and Dr. Y. Lu at University of Illinois at Urbana-Champaign, for their kind gift of Mb gene. NAMD and VMD were developed by the Theoretical Biophysics Group in the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign. This work was supported by the National Natural Science Foundation of China, NSFC (No. 31370812) and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry.

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Authors and Affiliations

  1. Institute of Cardiovascular Disease & Key Lab for Arteriosclerology of Human Province, University of South China, Hengyang, 421001, China

    Yong You, Fang Liu & Ge-Bo Wen

  2. School of Chemistry and Chemical Engineering, University of South China, Hengyang, 421001, China

    Ke-Jie Du & Ying-Wu Lin

  3. Laboratory of Protein Structure and Function, University of South China, Hengyang, 421001, China

    Ge-Bo Wen & Ying-Wu Lin

  4. School of Chemistry and Chemical Engineering, University of South China, Hengyang, 421001, China

    Ying-Wu Lin

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  1. Yong You
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  2. Fang Liu
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Correspondence to Ying-Wu Lin.

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You, Y., Liu, F., Du, KJ. et al. Structural and functional alterations of myoglobin by glucose-protein interactions. J Mol Model 20, 2358 (2014). https://doi.org/10.1007/s00894-014-2358-6

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  • DOI: https://doi.org/10.1007/s00894-014-2358-6

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