The Functional Structure of Human Serum Albumin

  • Matthias J. N. Junk
Part of the Springer Theses book series (Springer Theses)


Human serum albumin (HSA) is a versatile transport protein for various endogenous compounds and drugs. This study focuses on its highly relevant transport function for fatty acids in the circulatory system. While extensive crystallographic data on HSA–fatty acid binding exist, a new spectroscopic approach is used to gain information on the functional structure of HSA in solution. Using spin-labeled stearic acid and applying double electron–electron resonance (DEER) spectroscopy, the functional protein structure is accessed for the first time from the ligands’ point of view.


Electron Paramagnetic Resonance Human Serum Albumin Electron Paramagnetic Resonance Spectrum Pump Pulse Modulation Depth 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Peters T (1995) All about albumin: biochemistry genetics and medical applications. Academic, San DiegoGoogle Scholar
  2. 2.
    Carter DC, Ho JX (1994) Adv Protein Chem 45:153–203CrossRefGoogle Scholar
  3. 3.
    Spector AA (1975) J Lipid Res 16:165–179Google Scholar
  4. 4.
    Hamilton JA, Cistola DP, Morrisett JD, Sparrow JT, Small DM (1984) Proc Natl Acad Sci USA 81:3718–3722CrossRefGoogle Scholar
  5. 5.
    He XM, Carter DC (1992) Nature 358:209–215CrossRefGoogle Scholar
  6. 6.
    Curry S, Mandelkow H, Brick P, Franks N (1998) Nat Struct Biol 5:827–835CrossRefGoogle Scholar
  7. 7.
    Curry S, Brick P, Franks NP (1999) Biochim Biophys Acta Mol Cell Biol Lipids 1441:131–140Google Scholar
  8. 8.
    Bhattacharya AA, Grüne T, Curry S (2000) J Mol Biol 303:721–732CrossRefGoogle Scholar
  9. 9.
    Fasano M, Curry S, Terreno E, Galliano M, Fanali G, Narciso P, Notari S, Ascenzi P (2005) IUBMB Life 57:787–796Google Scholar
  10. 10.
    Hamilton JA, Era S, Bhamidipati SP, Reed RG (1991) Proc Natl Acad Sci USA 88:2051–2054CrossRefGoogle Scholar
  11. 11.
    Simard JR, Zunszain PA, Ha CE, Yang JS, Bhagavan NV, Petitpas I, Curry S, Hamilton JA (2005) Proc Natl Acad Sci USA 102:17958–17963CrossRefGoogle Scholar
  12. 12.
    Simard JR, Zunszain PA, Hamilton JA, Curry S (2006) J Mol Biol 361:336–351CrossRefGoogle Scholar
  13. 13.
    Henzler-Wildman K, Kern D (2007) Nature 450:964–972CrossRefGoogle Scholar
  14. 14.
    Lange OF, Lakomek N-A, Farès C, Schröder GF, Walter KFA, Becker S, Meiler J, Grubmüller H, Griesinger C, de Groot BL (2008) Science 320:1471–1475CrossRefGoogle Scholar
  15. 15.
    Salmon L, Bouvignies G, Markwick P, Lakomek N, Showalter S, Li D-W, Walter K, Griesinger C, Brüschweiler R, Blackledge M (2009) Angew Chem Int Ed 48:4154–4157CrossRefGoogle Scholar
  16. 16.
    Karush F (1950) J Am Chem Soc 72:2705–2713CrossRefGoogle Scholar
  17. 17.
    Karush F (1954) J Am Chem Soc 76:5536–5542CrossRefGoogle Scholar
  18. 18.
    Laiken N, Nemethy G (1971) Biochem 10:2101–2106CrossRefGoogle Scholar
  19. 19.
    Morrisett JD, Pownall HJ, Gotto AM (1975) J Biol Chem 250:2487–2494Google Scholar
  20. 20.
    Rehfeld SJ, Eatough DJ, Plachy WZ (1978) J Lipid Res 19:841–849Google Scholar
  21. 21.
    Livshits VA, Marsh D (2000) Biochim Biophys Acta Biomembr 1466:350–360CrossRefGoogle Scholar
  22. 22.
    Milov AD, Salikhov KM, Shirov MD (1981) Fiz Tverd Tela 23:975–982Google Scholar
  23. 23.
    Pannier M, Veit S, Godt A, Jeschke G, Spiess HW (2000) J Magn Reson 142:331–340CrossRefGoogle Scholar
  24. 24.
    Jeschke G, Pannier M, Spiess HW (2000) Double electron–electron resonance. In: Berliner LJ, Eaton GR, Eaton SS (eds) Biological magnetic resonance, vol 19: distance measurements in biological systems by EPR. Kluwer Academic, New YorkGoogle Scholar
  25. 25.
    Jeschke G (2002) Macromol Rapid Commun 23:227–246CrossRefGoogle Scholar
  26. 26.
    Hinderberger D, Schmelz O, Rehahn M, Jeschke G (2004) Angew Chem Int Ed 43:4616–4621CrossRefGoogle Scholar
  27. 27.
    Schiemann O, Prisner TF (2007) Q Rev Biophys 40:1–53CrossRefGoogle Scholar
  28. 28.
    Dockter C, Volkov A, Bauer C, Polyhach Y, Joly-Lopez Z, Jeschke G, Paulsen H (2009) Proc Natl Acad Sci USA 106:18485–18490CrossRefGoogle Scholar
  29. 29.
    Hilger D, Jung H, Padan E, Wegener C, Vogel KP, Steinhoff HJ, Jeschke G (2005) Biophys J 89:1328–1338CrossRefGoogle Scholar
  30. 30.
    Schiemann O, Piton N, Plackmeyer J, Bode BE, Prisner TF, Engels JW (2007) Nat Protoc 2:904–923CrossRefGoogle Scholar
  31. 31.
    Schiemann O, Cekan P, Margraf D, Prisner TF, Sigurdsson ST (2009) Angew Chem Int Ed 48:3292–3295CrossRefGoogle Scholar
  32. 32.
    Jeschke G, Sajid M, Schulte M, Godt A (2009) Phys Chem Chem Phys 11:6580–6591CrossRefGoogle Scholar
  33. 33.
    Schneider DJ, Freed JH (1989) Continuous-wave and pulsed ESR methods. In: Berliner LJ, Reuben J (eds) Biological magnetic resonance, vol 8: spin labeling–theory and applications. Plenum Press, New YorkGoogle Scholar
  34. 34.
    Stoll S, Schweiger A (2006) J Magn Reson 178:42–55CrossRefGoogle Scholar
  35. 35.
    Kawai K, Suzuki T, Oguni M (2006) Biophys J 90:3732–3738CrossRefGoogle Scholar
  36. 36.
    Inoue C, Ishikawa M (2000) J Food Sci 65:1187–1193CrossRefGoogle Scholar
  37. 37.
    Rariy RV, Klibanov AM (1997) Proc Natl Acad Sci USA 94:13520–13523CrossRefGoogle Scholar
  38. 38.
    Milov AD, Ponomarev AB, Tsvetkov YD (1984) Chem Phys Lett 110:67–72CrossRefGoogle Scholar
  39. 39.
    Bode BE, Margraf D, Planckmeyer J, Dürner G, Prisner TF, Schiemann O (2007) J Am Chem Soc 129:6736–6745CrossRefGoogle Scholar
  40. 40.
    Godt A, Franzen C, Veit S, Enkelmann V, Pannier M, Jeschke G (2000) J Org Chem 65:7575–7582CrossRefGoogle Scholar
  41. 41.
    Jeschke G, Chechik V, Ionita P, Godt A, Zimmermann H, Banham J, Timmel CR, Hilger D, Jung H (2006) Appl Magn Reson 30:473–498CrossRefGoogle Scholar
  42. 42.
    Polyhach Y, Godt A, Bauer C, Jeschke G (2007) J Magn Reson 185:118–129CrossRefGoogle Scholar
  43. 43.
    Curry S (2009) Drug Metab Pharmacokinet 24:342–357CrossRefGoogle Scholar
  44. 44.
    Zunszain PA, Ghuman J, Komatsu T, Tsuchida E, Curry S 2003 BMC Struct. Biol. 3: 6, doi:10.1186/1472
  45. 45.
    Zunszain PA, Ghuman J, McDonagh AF, Curry S (2008) J Mol Biol 381:394–406CrossRefGoogle Scholar
  46. 46.
    Wardell M, Wang ZM, Ho JX, Robert J, Ruker F, Ruble J, Carter DC (2002) Biochem Biophys Res Commun 291:813–819CrossRefGoogle Scholar
  47. 47.
    Petitpas I, Petersen CE, Ha CE, Bhattacharya AA, Zunszain PA, Ghuman J, Bhagavan NV, Curry S (2003) Proc Natl Acad Sci USA 100:6440–6445CrossRefGoogle Scholar
  48. 48.
    Narr E, Godt A, Jeschke G (2002) Angew Chem Int Ed 41:3907–3910CrossRefGoogle Scholar
  49. 49.
    van Amsterdam IMC, Ubbink M, Canters GW, Huber M (2003) Angew Chem Int Ed 42:62–64CrossRefGoogle Scholar
  50. 50.
    Larsen RG, Singel DJ (1993) J Chem Phys 98:5134–5146CrossRefGoogle Scholar
  51. 51.
    Maryasov AG, Tsvetkov YD, Raap J (1998) Appl Magn Reson 14:101–113CrossRefGoogle Scholar
  52. 52.
    Hertel MM, Denysenkov VP, Bennati M, Prisner TF (2005) Magn Reson Chem 43:S248–S255CrossRefGoogle Scholar
  53. 53.
    Denysenkov VP, Prisner TF, Stubbe J, Bennati M (2006) Proc Natl Acad Sci USA 103:13386–13390CrossRefGoogle Scholar
  54. 54.
    Denysenkov VP, Biglino D, Lubitz W, Prisner TF, Bennati M (2008) Angew Chem Int Ed 47:1224–1227CrossRefGoogle Scholar
  55. 55.
    Savitsky A, Dubinskii AA, Flores M, Lubitz W, Möbius K (2007) J Phys Chem B 111:6245–6262CrossRefGoogle Scholar
  56. 56.
    Margraf D, Bode BE, Marko A, Schiemann O, Prisner TF (2007) Mol Phys 105:2153–2160CrossRefGoogle Scholar
  57. 57.
    Bode BE, Plackmeyer J, Prisner TF, Schiemann O (2008) J Phys Chem A 112:5064–5073CrossRefGoogle Scholar
  58. 58.
    Kay CWM, El Mkami H, Cammack R, Evans RW (2007) J Am Chem Soc 129:4868–4869CrossRefGoogle Scholar
  59. 59.
    Yang Z, Becker J, Saxena S (2007) J Magn Reson 188:337–343CrossRefGoogle Scholar
  60. 60.
    Lovett JE, Bowen AM, Timmel CR, Jones MW, Dilworth JR, Caprotti D, Bell SG, Wong LL, Harmer J (2009) Phys Chem Chem Phys 11:6840–6848CrossRefGoogle Scholar
  61. 61.
    Cunningham KL, McNett KM, Pierce RA, Davis KA, Harris HH, Falck DM, McMillin DR (1997) Inorg Chem 36:608–613CrossRefGoogle Scholar
  62. 62.
    Jeschke G, Bender A, Paulsen H, Zimmermann H, Godt A (2004) J Magn Reson 169:1–12CrossRefGoogle Scholar
  63. 63.
    Hyde JS, Pasenkiewicz-Gierula M, Jesmanowicz A, Antholine WE (1990) Appl Magn Reson 1:483–496CrossRefGoogle Scholar
  64. 64.
    Krieger E, Darden T, Nabuurs SB, Finkelstein A, Vriend G (2004) Proteins 57:678–683CrossRefGoogle Scholar
  65. 65.
    Junk MJN, Spiess HW, Hinderberger D (2010) Angew Chem 122:8937–8941Google Scholar
  66. 66.
    Junk MJN, Spiess HW, Hinderberger D (2010) Angew Chem Int Ed 49:8755–8759CrossRefGoogle Scholar
  67. 67.
    Junk MJN, Spiess HW, Hinderberger D (2011) J Magn Reson 210:210–217CrossRefGoogle Scholar
  68. 68.
    Junk MJN, Spiess HW, Hinderberger D (2011) Biophys J 100:2293–2301CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Max Planck Institute for Polymer ResearchMainzGermany

Personalised recommendations