5D4A

Crystal Structure of FABP4 in complex with 3-(2-phenyl-1H-indol-1-yl)propanoic acid

Summary for 5D4A

• Entry DOI: 10.2210/pdb5d4a/pdb
• Related: 5D45 5D47 5D48
• Descriptor: Fatty acid-binding protein, adipocyte, 3-(2-phenyl-1H-indol-1-yl)propanoic acid (3 entities in total)
• Functional Keywords: fatty acid binding protein, lipid binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 17176.57

Authors

Tagami, U.,Takahashi, K.,Igarashi, S.,Ejima, C.,Yoshida, T.,Takeshita, S.,Miyanaga, W.,Sugiki, M.,Tokumasu, M.,Hatanaka, T.,Kashiwagi, T.,Ishikawa, K.,Miyano, H.,Mizukoshi, T. (deposition date: 2015-08-07, release date: 2016-06-22, Last modification date: 2023-11-08)

Primary citation

Tagami, U.,Takahashi, K.,Igarashi, S.,Ejima, C.,Yoshida, T.,Takeshita, S.,Miyanaga, W.,Sugiki, M.,Tokumasu, M.,Hatanaka, T.,Kashiwagi, T.,Ishikawa, K.,Miyano, H.,Mizukoshi, T.
Interaction Analysis of FABP4 Inhibitors by X-ray Crystallography and Fragment Molecular Orbital Analysis
Acs Med.Chem.Lett., 7:435-439, 2016

PubMed Abstract: X-ray crystal structural determination of FABP4 in complex with four inhibitors revealed the complex binding modes, and the resulting observations led to improvement of the inhibitory potency of FABP4 inhibitors. However, the detailed structure-activity relationship (SAR) could not be explained from these structural observations. For a more detailed understanding of the interactions between FABP4 and inhibitors, fragment molecular orbital analyses were performed. These analyses revealed that the total interfragment interaction energies of FABP4 and each inhibitor correlated with the ranking of the K i value for the four inhibitors. Furthermore, interactions between each inhibitor and amino acid residues in FABP4 were identified. The oxygen atom of Lys58 in FABP4 was found to be very important for strong interactions with FABP4. These results might provide useful information for the development of novel potent FABP4 inhibitors.

PubMed: 27096055
DOI: 10.1021/acsmedchemlett.6b00040

Experimental method

X-RAY DIFFRACTION (1.7 Å)