4J28

Crystal structure of a gh29 alpha-l-fucosidase gh29 from bacteroides thetaiotaomicron in complex with a 5-membered iminocyclitol inhibitor

Summary for 4J28

• Entry DOI: 10.2210/pdb4j28/pdb
• Related: 4J27 4JFS 4JFT 4JFU 4JFV 4JFW 4JL1 4JL2
• Descriptor: Alpha-L-fucosidase, (2S,3S,4R,5S)-2-(1H-benzimidazol-2-yl)-5-methylpyrrolidine-3,4-diol, IMIDAZOLE, ... (6 entities in total)
• Functional Keywords: alpha-l-fucosidase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Bacteroides Thetaiotaomicron
• Total number of polymer chains: 2
• Total formula weight: 105611.34

Authors

Wright, D.W. (deposition date: 2013-02-04, release date: 2013-05-08, Last modification date: 2023-09-20)

Primary citation

Wright, D.W.,Moreno-Vargas, A.J.,Carmona, A.T.,Robina, I.,Davies, G.J.
Three dimensional structure of a bacterial alpha-l-fucosidase with a 5-membered iminocyclitol inhibitor.
Bioorg.Med.Chem., 21:4751-4754, 2013

PubMed Abstract: Fucosidases, enzymes that cleave fucose from the non-reducing end of a glycan, represent promising medicinal targets reflecting their roles in cancer metastasis, inflammation, host-parasite interactions and the lysosomal storage disorder fucosidosis. The X-ray crystal structures of Bacteroides thetaiotaomicron GH29 α-l-fucosidase (BtFuc2970) in a new crystal form (at a resolution of 1.59Å) and liganded with a 5-membered iminocyclitol inhibitor (1.73Å) are reported herein. The 5-membered iminocyclitol binds in a (3)E conformation, mimicking the proposed (3)H4 half chair transition-state of the enzyme catalysed reaction, and its Ki for BtFuc2970 was determined as 2μM. Structural analysis of fucosidase inhibition through 5-membered iminocyclitols will aid in the rational design of more potent fucosidase inhibitors for treatment of a range of medical conditions.

PubMed: 23830696
DOI: 10.1016/j.bmc.2013.05.056

Experimental method

X-RAY DIFFRACTION (1.73 Å)