PDBsum entry 2j25

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Hydrolase PDB id
Protein chain
497 a.a.
SO4 ×17
Waters ×68

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Key reference
Title Structural comparison of differently glycosylated forms of acid-Beta-Glucosidase, The defective enzyme in gaucher disease.
Authors B.Brumshtein, M.R.Wormald, I.Silman, A.H.Futerman, J.L.Sussman.
Ref. Acta Crystallogr D Biol Crystallogr, 2006, 62, 1458-1465. [DOI no: 10.1107/S0907444906038303]
PubMed id 17139081
Gaucher disease is caused by mutations in the gene encoding acid-beta-glucosidase. A recombinant form of this enzyme, Cerezyme((R)), is used to treat Gaucher disease patients by ;enzyme-replacement therapy'. Crystals of Cerezyme((R)) after its partial deglycosylation were obtained earlier and the structure was solved to 2.0 A resolution [Dvir et al. (2003), EMBO Rep. 4, 704-709]. The crystal structure of unmodified Cerezyme((R)) is now reported, in which a substantial number of sugar residues bound to three asparagines via N-glycosylation could be visualized. The structure of intact fully glycosylated Cerezyme((R)) is virtually identical to that of the partially deglycosylated enzyme. However, the three loops at the entrance to the active site, which were previously observed in alternative conformations, display additional variability in their structures. Comparison of the structure of acid-beta-glucosidase with that of xylanase, a bacterial enzyme from a closely related protein family, demonstrates a close correspondence between the active-site residues of the two enzymes.
Figure 6.
Figure 6 Putative membrane binding sites in crystal structures of GlcCerase. Catalytic residues are shown in red and loops 1-3 in green. Substrate binding was modelled according to Dvir et al. (2003[Dvir, H., Harel, M., McCarthy, A. A., Toker, L., Silman, I., Futerman, A. H. & Sussman, J. L. (2003). EMBO Rep. 4, 704-709.]) and shown in yellow. (a) Some of the sulfates are shown in space-filling representation in red. (b) Side-on view [rotated 90° around the horizontal axis relative to (a)] of a putative mode of binding of GlcCerase to negatively charged phospholipids.
Figure 7.
Figure 7 Comparison of the active sites of GCase and xylanase. Residues within a 5 Å radius of the active site are displayed. Yellow, 2j25-A (GCase); green, 2j25-B; blue, 1nof (xylanase); orange, 1ogs-A (pDG-GCase); red, 1ogs-B; black, 2f61-A (pDG-GCase); grey, 2f61-B. The first number refers to residue in GCase and the second number to the corresponding residue in xylanase.
The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2006, 62, 1458-1465) copyright 2006.
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