5ABF

Structure of GH84 with ligand

Summary for 5ABF

• Entry DOI: 10.2210/pdb5abf/pdb
• Related: 5ABE 5ABG 5ABH
• Descriptor: O-GLCNACASE BT_4395, 1,2-ETHANEDIOL, 2-[(2S,3R,4R,5R)-5-(hydroxymethyl)-3,4-bis(oxidanyl)-1-pentyl-pyrrolidin-2-yl]-N-methyl-ethanamide, ... (6 entities in total)
• Functional Keywords: hydrolase, tim-barrel, inhibitor
• Biological source: BACTEROIDES THETAIOTAOMICRON; More
• Total number of polymer chains: 2
• Total formula weight: 167741.75

Authors

Bergeron-Brlek, M.,Goodwin-Tindall, J.,Cekic, N.,Varghese, V.,Zandberg, W.F.,Shan, X.,Roth, C.,Chan, S.,Davies, G.J.,Vocadlo, D.J.,Britton, R. (deposition date: 2015-08-05, release date: 2015-11-18, Last modification date: 2024-05-08)

Primary citation

Bergeron-Brlek, M.,Goodwin-Tindall, J.,Cekic, N.,Roth, C.,Zandberg, W.F.,Shan, X.,Varghese, V.,Chan, S.,Davies, G.J.,Vocadlo, D.J.,Britton, R.
A Convenient Approach to Stereoisomeric Iminocyclitols: Generation of Potent Brain-Permeable Oga Inhibitors.
Angew.Chem.Int.Ed.Engl., 54:15429-, 2015

PubMed Abstract: Pyrrolidine-based iminocyclitols are a promising class of glycosidase inhibitors. Reported herein is a convenient epimerization strategy that provides direct access to a range of stereoisomeric iminocyclitol inhibitors of O-GlcNAcase (OGA), the enzyme responsible for catalyzing removal of O-GlcNAc from nucleocytoplasmic proteins. Structural details regarding the binding of these inhibitors to a bacterial homologue of OGA reveal the basis for potency. These compounds are orally available and permeate into rodent brain to increase O-GlcNAc, and should prove useful tools for studying the role of OGA in health and disease.

PubMed: 26545827
DOI: 10.1002/ANIE.201507985

Experimental method

X-RAY DIFFRACTION (2.1 Å)