1j4i
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| , resolution 1.8Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Peptidylprolyl isomerase, with EC number 5.2.1.8 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
crystal structure analysis of the FKBP12 complexed with 000308 small molecule
OverviewOverview
Based on the structure of FKBP12 complexed with FK506 or rapamycin, with computer-aided design, two neurotrophic ligands, (3R)-4-(p-Toluenesulfonyl)-1,4-thiazane-3-carboxylic acid-L-Leucine ethyl ester and (3R)-4-(p-Toluenesulfonyl)-1,4-thiazane-3-carboxylic acid-L-phenylalanine benzyl ester, were designed and synthesized. Fluorescence experiments were used to detect the binding affinity between FKBP12 and these two ligands. Complex structures of FKBP12 with these two ligands were obtained by x-ray crystallography. In comparing FKBP12-rapamycin complex and FKBP12-FK506 complex as well as FKBP12-GPI-1046 solution structure with these new complexes, significant volume and surface area effects and obvious contact changes were detected which are expected to cause their different binding energies-showing these two novel ligands will become more effective neuron regeneration drugs than GPI-1046, which is currently undergoing phase II clinical trail as a neurotrophic drug. Analysis of volume and surface area effects also gives a new clue for structure-based drug design.
About this StructureAbout this Structure
1J4I is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Design and structure-based study of new potential FKBP12 inhibitors., Sun F, Li P, Ding Y, Wang L, Bartlam M, Shu C, Shen B, Jiang H, Li S, Rao Z, Biophys J. 2003 Nov;85(5):3194-201. PMID:14581219
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