 |
PDBsum entry 1j4h
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Design and structure-Based study of new potential fkbp12 inhibitors.
|
|
|
Authors
|
|
F.Sun,
P.Li,
Y.Ding,
L.Wang,
M.Bartlam,
C.Shu,
B.Shen,
H.Jiang,
S.Li,
Z.Rao.
|
|
|
Ref.
|
|
Biophys J, 2003,
85,
3194-3201.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
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.
|
|
|
|
|
|
|
