6TBJ

Structure of a beta galactosidase with inhibitor

Summary for 6TBJ

• Entry DOI: 10.2210/pdb6tbj/pdb
• Descriptor: Beta-galactosidase, putative, bgl35A, SODIUM ION, 5-(dimethylamino)-~{N}-[6-[(2~{S},3~{R},4~{S},5~{R})-3-(hydroxymethyl)-4,5-bis(oxidanyl)piperidin-2-yl]hexyl]naphthalene-1-sulfonamide, ... (4 entities in total)
• Functional Keywords: beta galactosidase, inhibitor, hydrolase
• Biological source: Cellvibrio japonicus Ueda107
• Total number of polymer chains: 8
• Total formula weight: 501473.98

Authors

Offen, W.,Davies, G. (deposition date: 2019-11-01, release date: 2020-08-19, Last modification date: 2024-01-24)

Primary citation

Weber, P.,Thonhofer, M.,Averill, S.,Davies, G.J.,Santana, A.G.,Muller, P.,Nasseri, S.A.,Offen, W.A.,Pabst, B.M.,Paschke, E.,Schalli, M.,Torvisco, A.,Tschernutter, M.,Tysoe, C.,Windischhofer, W.,Withers, S.G.,Wolfsgruber, A.,Wrodnigg, T.M.,Stutz, A.E.
Mechanistic Insights into the Chaperoning of Human Lysosomal-Galactosidase Activity: Highly Functionalized Aminocyclopentanes and C -5a-Substituted Derivatives of 4- epi -Isofagomine.
Molecules, 25:-, 2020

PubMed Abstract: Glycosidase inhibitors have shown great potential as pharmacological chaperones for lysosomal storage diseases. In light of this, a series of new cyclopentanoid β-galactosidase inhibitors were prepared and their inhibitory and pharmacological chaperoning activities determined and compared with those of lipophilic analogs of the potent β-d-galactosidase inhibitor 4--isofagomine. Structure-activity relationships were investigated by X-ray crystallography as well as by alterations in the cyclopentane moiety such as deoxygenation and replacement by fluorine of a "strategic" hydroxyl group. New compounds have revealed highly promising activities with a range of β-galactosidase-compromised human cell lines and may serve as leads towards new pharmacological chaperones for G-gangliosidosis and Morquio B disease.

PubMed: 32899288
DOI: 10.3390/molecules25174025

Experimental method

X-RAY DIFFRACTION (1.5 Å)