3FMZ

Crystal Structure of Retinol-Binding Protein 4 (RBP4) in complex with non-retinoid ligand

Summary for 3FMZ

• Entry DOI: 10.2210/pdb3fmz/pdb
• Descriptor: Retinol-binding protein 4, 2-[({4-[2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)amino]benzoic acid (3 entities in total)
• Functional Keywords: retinol binding, disease mutation, retinol-binding, secreted, sensory transduction, transport, vision, vitamin a, transport protein
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted: P02753
• Total number of polymer chains: 2
• Total formula weight: 50025.70

Authors

Wang, Z.,Johnstone, S.,Walker, N.P. (deposition date: 2008-12-22, release date: 2009-01-27, Last modification date: 2024-10-16)

Primary citation

Motani, A.,Wang, Z.,Conn, M.,Siegler, K.,Zhang, Y.,Liu, Q.,Johnstone, S.,Xu, H.,Thibault, S.,Wang, Y.,Fan, P.,Connors, R.,Le, H.,Xu, G.,Walker, N.,Shan, B.,Coward, P.
Identification and Characterization of a Non-retinoid Ligand for Retinol-binding Protein 4 Which Lowers Serum Retinol-binding Protein 4 Levels in Vivo.
J.Biol.Chem., 284:7673-7680, 2009

PubMed Abstract: Retinol-binding protein 4 (RBP4) transports retinol from the liver to extrahepatic tissues, and RBP4 lowering is reported to improve insulin sensitivity in mice. We have identified A1120, a high affinity (K(i) = 8.3 nm) non-retinoid ligand for RBP4, which disrupts the interaction between RBP4 and its binding partner transthyretin. Analysis of the RBP4-A1120 co-crystal structure reveals that A1120 induces critical conformational changes at the RBP4-transthyretin interface. Administration of A1120 to mice lowers serum RBP4 and retinol levels but, unexpectedly, does not improve insulin sensitivity. In addition, we show that Rpb4(-/-) mice display normal insulin sensitivity and are not protected from high fat diet-induced insulin resistance. We conclude that lowering RBP4 levels does not improve insulin sensitivity in mice. Therefore, RBP4 lowering may not be an effective strategy for treating diabetes.

PubMed: 19147488
DOI: 10.1074/jbc.M809654200

Experimental method

X-RAY DIFFRACTION (2.9 Å)