2osx
From Proteopedia
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Endo-glycoceramidase II from Rhodococcus sp.: Ganglioside GM3 Complex
Overview
endo-Glycoceramidase, a membrane-associated family 5 glycosidase, deviates, from the typical polysaccharide substrate specificity of other soluble, members of the family, preferentially hydrolyzing glycosidic linkages, between the oligosaccharide and ceramide moieties of gangliosides. Here we, report the first x-ray crystal structures of an endo-glycoceramidase from, Rhodococcus sp., in the apo form, in complex with the ganglioside G(M3), (Svennerholm ganglioside nomenclature (Svennerholm, L. (1964) J. Lipid, Res. 5, 145-155)), and trapped as a glycosyl-enzyme intermediate. These, snapshots provide the first molecular insight into enzyme recognition and, association with gangliosides, revealing the structural adaptations, necessary for glycosidase-catalyzed hydrolysis and detailing a novel, ganglioside binding topology. Consistent with the chemical duality of the, substrate, the active site of endo-glycoceramidase is split into a wide, polar cavity to bind the polyhydroxylated oligosaccharide moiety and a, narrow, hydrophobic tunnel to bind the ceramide lipid chains. The specific, interactions with the ceramide polar head group manifest a surprising, aglycone specificity, an observation substantiated by our kinetic, analyses. Collectively, the reported structural and kinetic data provide, insight toward rational redesign of the synthetic glycosynthase mutant of, endo-glycoceramidase to enable facile synthesis of nonnatural, therapeutically useful gangliosides.
About this Structure
2OSX is a Single protein structure of sequence from Rhodococcus sp. with , and as ligands. Active as Endoglycosylceramidase, with EC number 3.2.1.123 Full crystallographic information is available from OCA.
Reference
Structural and mechanistic analyses of endo-glycoceramidase II, a membrane-associated family 5 glycosidase in the Apo and GM3 ganglioside-bound forms., Caines ME, Vaughan MD, Tarling CA, Hancock SM, Warren RA, Withers SG, Strynadka NC, J Biol Chem. 2007 May 11;282(19):14300-8. Epub 2007 Feb 28. PMID:17329247
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