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FABP1: Human liver fatty acid binding protein 1

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PDB Code 2F73 Target Class Lipid signalling Target FABP1 Alias FABP1, FABPL, L-FABP Disease Area/Function metabolism Date Deposited Nov 30 2005 Authors P.KURSULA, A.G.THORSELL, C.ARROWSMITH, H.BERGLUND, A.EDWARDS, M.EHN, S.FLODIN, S.GRASLUND, M.HAMMARSTROM, L.HOLMBERGSCHIAVONE, T.KOTENYOVA, P.NILSSON-EHLE, P.NORDLUND, T.NYMAN, D.OGG, C.PERSSON, J.SAGEMARK, P.STENMARK, M.SUNDSTROM, S.VAN DENBERG, J.WEIGELT, B.M.HALLBERG, STRUCTURAL GENOMICS CONSORTIUM(SGC)

About this structure

Given the low aqueous solubility of fatty acids, their transport in the cell needs to be mediated by specific binding proteins. Liver fatty-acid-binding protein (FABP1) is found in high abundance in the hepatocyte cytosol, but associates also in the hepatocyte nucleus in a specific ligand-dependent manner. It facilitates the cellular uptake, transport and metabolism of fatty acids and is involved in the regulation of gene expressions and cell differentiation. FABP1 belongs to the family of intracellular lipid binding proteins, having a 10-stranded â-clam structure confining a lipid-binding cavity gated by two short anti-parallell helices; however, FABP1 is unique in this family in that the ligand pocket is unusually large and therefore capable of binding two molar equivalents of long-chain fatty acids and also larger ligands such as heme.

FABP1 binding and transport of peroxisome proliferators, especially leukotriene D4 antagonists, are implicated in side-effects of anti-inflammatory asthma therapy.

References

Cannon, JR & Eacho, PI (1999). Interaction of LY171883 and peroxisome proliferators with fatty–acid-binding protein isolated from rat liver (1991). Biochem. J., 280, 387-391.

Thompson, J, Reese-Wagoner, A & Banaszak, L.. Liver fatty acid binding protein: species variation and the accommodation of different ligands. BBA, 1441, 117-130.

Thompson J, Winter N, Terwey D, Bratt J & Banaszak L. (1997). The crystal structure of liver fatty-acid-binding protein. JBC, 272, 7140-7150.

Lawrence JW, Kroll, DJ & Eacho PI (2000). Ligand-dependent interaction of hepatic fatty-acid binding protein with the nucleus. J. Lipid. Res., 41, 1390-1401.