3FU5: Leukotriene A4 hydrolase in complex with (5-thiophen-2-ylthiophen-2-yl)methylamine

Citation:
Abstract
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.
PDB ID: 3FU5Download
MMDB ID: 75613
PDB Deposition Date: 2009/1/14
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.3  Å
Source Organism:
Similar Structures:
Biological Unit for 3FU5: monomeric; determined by author and by software (PISA)
Molecular Components in 3FU5
Label Count Molecule
Protein (1 molecule)
1
Leukotriene A-4 Hydrolase(Gene symbol: LTA4H)
Molecule annotation
Chemicals (6 molecules)
1
1
2
1
3
1
4
1
5
2
* Click molecule labels to explore molecular sequence information.

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