1f40
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1fkj|1fkj]], [[1fkg|1fkg]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1f40 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f40 OCA], [http://www.ebi.ac.uk/pdbsum/1f40 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1f40 RCSB]</span> | ||
}} | }} | ||
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[[Category: Sich, C.]] | [[Category: Sich, C.]] | ||
[[Category: Teufel, M.]] | [[Category: Teufel, M.]] | ||
| - | [[Category: GPI]] | ||
[[Category: isomerase]] | [[Category: isomerase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:15:22 2008'' |
Revision as of 17:15, 30 March 2008
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| Ligands: | |||||||
| Related: | 1fkj, 1fkg
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
SOLUTION STRUCTURE OF FKBP12 COMPLEXED WITH GPI-1046, A NEUROTROPHIC LIGAND
Overview
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.
About this Structure
1F40 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
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