2osw

[[Image:2osw.jpg|left|200px]]<br /><applet load="2osw" size="350" color="white" frame="true" align="right" spinBox="true"

caption="2osw, resolution 1.600&Aring;" />

'''Endo-glycoceramidase II from Rhodococcus sp.'''<br />

==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==

2OSW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rhodococcus_sp. Rhodococcus sp.] with <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=TRS:'>TRS</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Endoglycosylceramidase Endoglycosylceramidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.123 3.2.1.123] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OSW 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17329247 17329247]

[[Category: Rhodococcus sp.]]

[[Category: Single protein]]

[[Category: Caines, M.E.C.]]

[[Category: Strynadka, N.C.J.]]

[[Category: NA]]

[[Category: TRS]]

[[Category: (alpha/beta)8 (tim) barrel]]

 

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