Fatty acids are important substrates for the synthesis of membrane phospholipids and other bioactive compounds, and thus play vital roles in mammalian energy metabolism. Fatty acids often bind to proteins in the blood. Albumin is a major carrier and depot of free fatty acids. In this paper, the interactions between human serum albumin (HSA) and fatty acids were studied using nuclear magnetic resonance (NMR)-based histidine selective detection technology T2W-RD-WaterLOGSY. The spectra of HSA before and after fatty acids binding were compared. It was found that signals of the characterized His in HSA changed significantly with the addition of fatty acids. Two high-affinity binding sites between the HSA and fatty acids were identified from the titration curve. It was also demonstrated that binding to fatty acids could induce conformation changes for HSA.
GAO Dong-li
,
SUN Peng
,
WANG Qian-wen
,
LIU Mai-li
,
ZHANG Xu
. Interactions Between Albumin and Fatty Acids Studied by NMR Spectroscopy[J]. Chinese Journal of Magnetic Resonance, 2018
, 35(3)
: 338
-344
.
DOI: 10.11938/cjmr20182641
[1] SLEEP D. Albumin and its application in drug delivery[J]. Expert Opin Drug Deliv, 2015, 12(5):793-812.
[2] KENDALL F E. Studies on human serum proteins[J]. J Biol Chem, 1941, 138(1):97-109.
[3] SUGIO S, KASHIMA A, MOCHIZUKI S, et al. Crystal structure of human serum albumin at 2.5Å resolution[J]. Protein Eng Des Sel, 1999, 12(6):439-446.
[4] FREDRICKSON D S, JR R S G. The metabolism of albumin-bound C14-labeled unesterified fatty acids in normal human subjects[J]. J Clin Invest, 1958, 37(11):1504-1515.
[5] LIAO S M, DU Q S, MENG J Z, et al. The multiple roles of histidine in protein interactions[J]. Chem Cent J, 2013, 7(1):44.
[6] SCHNEIDER F. Histidine in enzyme active centers[J]. Angew Chem Int Ed Engl, 1978, 17(8):583-592.
[7] BLINDAUER C A, HARVEY I, BUNYAN K E, et al. Structure, properties, and engineering of the major zinc binding site on human albumin[J]. J Biol Chem, 2009, 284(34):23116-23124.
[8] KANEKO K, CHUANG V T, MINOMO A, et al. Histidine146 of human serum albumin plays a prominent role at the interface of subdomains IA and ⅡA in allosteric ligand binding[J]. IUBMB Life, 2011, 63(4):277-285.
[9] BHATTACHARYA A A, GRüNE T, CURRY S. Crystallographic analysis reveals common modes of binding of medium and long-chain fatty acids to human serum albumin[J]. J Mol Biol, 2000, 303(5):721-732.
[10] DAI C Y, ZHANG Z T, LIU M L, et al. Application of NMR in the studies of structure and interactions of α-synuclein[J]. Chinese J Magn Reson, 2016, 33(1):153-167. 戴晨晔, 张则婷, 刘买利, 等. NMR在α-Synuclein的结构及相互作用研究中的应用[J]. 波谱学杂志, 2016, 33(1):153-167.
[11] CHENG K, YAO C D, XU G H, et al. Interaction of GB1 with metal ions studied by NMR spectroscopy[J]. Chinese J Magn Reson, 2018, 35(1):1-7. 成凯, 姚陈叠, 徐国华, 等. GB1与金属离子相互作用的NMR研究[J]. 波谱学杂志, 2018, 35(1):1-7.
[12] SIMARD J R, ZUNSZAIN P A, HAMILTON J A, et al. Location of high and low affinity fatty acid binding sites on human serum albumin revealed by NMR drug-competition analysis[J]. J Mol Biol, 2006, 361(2):336-351.
[13] HAMILTON J A. NMR reveals molecular interactions and dynamics of fatty acid binding to albumin[J]. Biochim Biophys Acta, 2013, 1830(12):5418-5426.
[14] DALVIT C, PEVARELLO P, TATÒ M, et al. Identification of compounds with binding affinity to proteins via magnetization transfer from bulk water[J]. J Biomol NMR, 2000, 18(1):65-68.
[15] DALVIT C, FOGLIATTO G, STEWART A, et al. WaterLOGSY as a method for primary NMR screening:practical aspects and range of applicability[J]. J Biomol NMR, 2001, 21(4):349-359.
[16] SUN P, JIANG X W, JIANG B, et al. Biomolecular ligands screening using radiation damping difference WaterLOGSY spectroscopy[J]. J Biomol NMR, 2013, 56(3):285-290.
[17] CHEN Y, SUN P, LIU M L, et al. Effects of metal ions on human serum albumin studied by radiation damping water-ligand observed via gradient spectroscopy[J]. Chinese J Magn Reson, 2017, 34(3):266-274. 陈瑶, 孙鹏, 刘买利, 等. 离子对人血清白蛋白影响的1H NMR研究[J]. 波谱学杂志, 2017, 34(3):266-274.
[18] 陈瑶. 人血清白蛋白与配体之间相互作用的核磁共振研究[D]. 武汉:中国科学院武汉物理与数学研究所, 2016.
[19] FANALI G, DI MASI A, TREZZA V, et al. Human serum albumin:from bench to bedside[J]. Mol Aspects Med, 2012, 33(3):209-290.
[20] WOSILAIT W D, SOLER-ARGILAGA C. A theoretical analysis of the multiple binding of palmitate by bovine serum albumin:The relationship to uptake of free fatty acids by tissues[J]. Life Sci, 1975, 17(1):159-166.
[21] VAN DER VUSSE G J. Albumin as fatty acid transporter[J]. Drug Metab Pharmacokinet, 2009, 24(4):300-307.
