Summary
PDB 3FUF deposited: 2009-01-14 modified: 2009-09-15
Title Leukotriene A4 hydrolase in complex with fragment 5-fluoroindole and bestatin
Authors Burgin, A.B., Christensen, J., Davies, D.R., Gurney, M.E., Hansen, E., Haraldsson, M.H., Kim, H., Kiselyov, A.S., Magnusson, O.T., Mamat, B., Mishra, R., Pease, B., Singh, J., Stewart, L.J., Zembower, D.
Method X-RAY DIFFRACTION
Structure factors resolution 2.6 rfactor 0.186 rfree 0.251
DPI 0.87 theoretical min: 0.39
Related PDB Entries 3FTS 3FTU 3FTV 3FTW 3FTX 3FTY 3FU0 3FU3 3FU5 3FU6 3FUD 3FUE 3FUH 3FUI 3FUJ 3FUK 3FUM 3FUN
Citations

We describe a novel fragment library termed fragments of life (FOL) for structure-based drug discovery. The FOL library includes natural small molecules of life, derivatives thereof, and biaryl protein architecture mimetics. The choice of fragments facilitates the interrogation of protein active sites, allosteric binding sites, and protein-protein interaction surfaces for fragment binding. We screened the FOL library against leukotriene A4 hydrolase (LTA4H) by X-ray crystallography. A diverse set of fragments including derivatives of resveratrol, nicotinamide, and indole were identified as efficient ligands for LTA4H. These fragments were elaborated in a small number of synthetic cycles into potent inhibitors of LTA4H representing multiple novel chemotypes for modulating leukotriene biosynthesis. Analysis of the fragment-bound structures also showed that the fragments comprehensively recapitulated key chemical features and binding modes of several reported LTA4H inhibitors.

J.Med.Chem. 2009 Aug; 52(15):4694-4715 doi:10.1021/jm900259h

Cross References
Database source Identifier Description
ChEMBL Document CHEMBL1158490
PubMed 19618939 JMCMAR
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
3FUF/0 3FUF 0 monomer 0 1 7 4238