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1f40

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1f40, 10 NMR models ()
Ligands:
Related: 1fkj, 1fkg
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

SOLUTION STRUCTURE OF FKBP12 COMPLEXED WITH GPI-1046, A NEUROTROPHIC LIGAND

Publication Abstract from PubMed

The structure of a recently reported neurotrophic ligand, 3-(3-pyridyl)-1-propyl(2S)-1-(3,3-dimethyl-1, 2-dioxopentyl)-2-pyrrolidinecarboxylate, in complex with FKBP12 was determined using heteronuclear NMR spectroscopy. The inhibitor exhibits a binding mode analogous to that observed for the macrocycle FK506, used widely as an immunosuppressant, with the prolyl ring replacing the pipecolyl moiety and the amide bond in a trans conformation. However, fewer favourable protein-ligand interactions are detected in the structure of the complex, suggesting weaker binding compared with the immunosuppressant drug. Indeed, a micromolar dissociation constant was estimated from the NMR ligand titration profile, in contrast to the previously published nanomolar inhibition activity. Although the inhibitor possesses a remarkable structural simplicity with respect to FK506, 15N relaxation studies show that it induces similar effects on the protein dynamics, stabilizing the conformation of solvent-exposed residues which are important for mediating the interaction of immunophilin/ligand complexes with molecular targets and potentially for the transmission of the neurotrophic action of FKBP12 inhibitors.

Solution structure of a neurotrophic ligand bound to FKBP12 and its effects on protein dynamics., Sich C, Improta S, Cowley DJ, Guenet C, Merly JP, Teufel M, Saudek V, Eur J Biochem. 2000 Sep;267(17):5342-55. PMID:10951192

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

1f40 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA.

See Also

Reference

  • Sich C, Improta S, Cowley DJ, Guenet C, Merly JP, Teufel M, Saudek V. Solution structure of a neurotrophic ligand bound to FKBP12 and its effects on protein dynamics. Eur J Biochem. 2000 Sep;267(17):5342-55. PMID:10951192

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