4PCT

Crystal structure of a bacterial fucosidase with iminocyclitol (2S,3S,4R,5S)-3,4-dihydroxy-2-ethynyl-5-methylpyrrolidine

Summary for 4PCT

• Entry DOI: 10.2210/pdb4pct/pdb
• Related: 4PCS
• Descriptor: Alpha-L-fucosidase, SULFATE ION, IMIDAZOLE, ... (5 entities in total)
• Functional Keywords: enzyme inhibition, hydrolase
• Biological source: Bacteroides thetaiotaomicron
• Total number of polymer chains: 4
• Total formula weight: 204907.67

Authors

Wright, D.W.,Davies, G.J. (deposition date: 2014-04-16, release date: 2014-07-02, Last modification date: 2023-12-20)

Primary citation

Hottin, A.,Wright, D.W.,Davies, G.J.,Behr, J.B.
Exploiting the Hydrophobic Terrain in Fucosidases with Aryl-Substituted Pyrrolidine Iminosugars.
Chembiochem, 16:277-283, 2015

PubMed Abstract: Fucosidase inhibition shows potential in numerous therapeutic contexts. Substitution of fucose-like iminosugars with hydrophobic "aglycons" yields significant improvements in potency of fucosidase inhibition. Here we have prepared three new 2-aryl-3,4-dihydroxy-5-methylpyrrolidines featuring phenyl substituents in variable orientations with respect to the iminocyclitol core and at various distances from it to explore the key binding interactions that stabilise the enzyme-inhibitor complex. The presence of a triazole linker in one structure resulted in nanomolar inhibition of the fucosidase from bovine kidney (Ki =4.8 nM), thus giving rise to one of the most potent pyrrolidine-type inhibitors of this enzyme known to date.

PubMed: 25427942
DOI: 10.1002/cbic.201402509

Experimental method

X-RAY DIFFRACTION (2.1 Å)