1f40: Difference between revisions
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[[Image:1f40.gif|left|200px]] | [[Image:1f40.gif|left|200px]] | ||
'''SOLUTION STRUCTURE OF FKBP12 COMPLEXED WITH GPI-1046, A NEUROTROPHIC LIGAND''' | {{Structure | ||
|PDB= 1f40 |SIZE=350|CAPTION= <scene name='initialview01'>1f40</scene> | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=GPI:(2S)-[3-PYRIDYL-1-PROPYL]-1-[3,3-DIMETHYL-1,2-DIOXOPENTYL]-2-PYRROLIDINECARBOXYLATE'>GPI</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''SOLUTION STRUCTURE OF FKBP12 COMPLEXED WITH GPI-1046, A NEUROTROPHIC LIGAND''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1F40 is a [ | 1F40 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F40 OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/10951192 10951192] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: isomerase]] | [[Category: isomerase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:04:04 2008'' | ||
Revision as of 09:04, 20 March 2008
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| Ligands: | GPI | ||||||||||||
| 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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