1J4H

crystal structure analysis of the FKBP12 complexed with 000107 small molecule

1J4H の概要

• エントリーDOI: 10.2210/pdb1j4h/pdb
• 関連するPDBエントリー: 1J4I
• 分子名称: FKBP12, 3-PHENYL-2-{[4-(TOLUENE-4-SULFONYL)-THIOMORPHOLINE-3-CARBONYL]-AMINO}-PROPIONIC ACID ETHYL ESTER (3 entities in total)
• 機能のキーワード: isomerase, rotamase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12313.12

構造登録者

Li, P.,Ding, Y.,Wang, L.,Wu, B.,Shu, C.,Li, S.,Shen, B.,Rao, Z. (登録日: 2001-09-30, 公開日: 2003-06-03, 最終更新日: 2023-12-27)

主引用文献

Sun, F.,Li, P.,Ding, Y.,Wang, L.,Bartlam, M.,Shu, C.,Shen, B.,Jiang, H.,Li, S.,Rao, Z.
Design and structure-based study of new potential FKBP12 inhibitors.
Biophys.J., 85:3194-3201, 2003

PubMed 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.

PubMed: 14581219
DOI: 10.1016/S0006-3495(03)74737-7

実験手法

X-RAY DIFFRACTION (1.8 Å)