1j4h
From Proteopedia
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crystal structure analysis of the FKBP12 complexed with 000107 small molecule
Overview
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 Structure
1J4H is a Single protein structure of sequence from Homo sapiens with SUB as ligand. Active as Peptidylprolyl isomerase, with EC number 5.2.1.8 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Mon Nov 12 17:37:14 2007
Categories: Homo sapiens | Peptidylprolyl isomerase | Single protein | Ding, Y. | Li, P. | Li, S. | Rao, Z. | Shen, B. | Shu, C. | Wang, L. | Wu, B. | SUB | Isomerase | Rotamase
