3JSQ

Crystal structure of adipocyte fatty acid binding protein non-covalently modified with 4-hydroxy-2-nonenal

Summary for 3JSQ

• Entry DOI: 10.2210/pdb3jsq/pdb
• Related: 3JS1
• Descriptor: Adipocyte fatty acid-binding protein, CHLORIDE ION, (2E,4R)-4-HYDROXYNON-2-ENAL, ... (5 entities in total)
• Functional Keywords: lipid binding protein, fatty acid binding protein
• Biological source: Mus musculus (mouse)
• Cellular location: Cytoplasm: P04117
• Total number of polymer chains: 1
• Total formula weight: 15111.25

Authors

Hellberg, K.,Grimsrud, P.A.,Kruse, A.C.,Banaszak, L.J.,Ohlendorf, D.H.,Bernlohr, D.A. (deposition date: 2009-09-10, release date: 2010-08-25, Last modification date: 2023-09-06)

Primary citation

Hellberg, K.,Grimsrud, P.A.,Kruse, A.C.,Banaszak, L.J.,Ohlendorf, D.H.,Bernlohr, D.A.
X-ray crystallographic analysis of adipocyte fatty acid binding protein (aP2) modified with 4-hydroxy-2-nonenal.
Protein Sci., 19:1480-1489, 2010

PubMed Abstract: Fatty acid binding proteins (FABP) have been characterized as facilitating the intracellular solubilization and transport of long-chain fatty acyl carboxylates via noncovalent interactions. More recent work has shown that the adipocyte FABP is also covalently modified in vivo on Cys117 with 4-hydroxy-2-nonenal (4-HNE), a bioactive aldehyde linked to oxidative stress and inflammation. To evaluate 4-HNE binding and modification, the crystal structures of adipocyte FABP covalently and noncovalently bound to 4-HNE have been solved to 1.9 A and 2.3 A resolution, respectively. While the 4-HNE in the noncovalently modified protein is coordinated similarly to a carboxylate of a fatty acid, the covalent form show a novel coordination through a water molecule at the polar end of the lipid. Other defining features between the two structures with 4-HNE and previously solved structures of the protein include a peptide flip between residues Ala36 and Lys37 and the rotation of the side chain of Phe57 into its closed conformation. Representing the first structure of an endogenous target protein covalently modified by 4-HNE, these results define a new class of in vivo ligands for FABPs and extend their physiological substrates to include bioactive aldehydes.

PubMed: 20509169
DOI: 10.1002/pro.427

Experimental method

X-RAY DIFFRACTION (2.3 Å)