1J4H

crystal structure analysis of the FKBP12 complexed with 000107 small molecule

Summary for 1J4H

• Entry DOI: 10.2210/pdb1j4h/pdb
• Related: 1J4I
• Descriptor: FKBP12, 3-PHENYL-2-{[4-(TOLUENE-4-SULFONYL)-THIOMORPHOLINE-3-CARBONYL]-AMINO}-PROPIONIC ACID ETHYL ESTER (3 entities in total)
• Functional Keywords: isomerase, rotamase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 12313.12

Authors

Li, P.,Ding, Y.,Wang, L.,Wu, B.,Shu, C.,Li, S.,Shen, B.,Rao, Z. (deposition date: 2001-09-30, release date: 2003-06-03, Last modification date: 2023-12-27)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.8 Å)