3buq

Golgi alpha-mannosidase II D204A catalytic nucleophile mutant with bound mannose.Golgi alpha-mannosidase II D204A catalytic nucleophile mutant with bound mannose.

Structural highlights 3buq is a 1 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , , Related: 1hty, 1hww, 1hxk, 1ps2, 1qwn, 1qwu, 1qx1, 1r33, 1r34, 1tqs, 1tqt, 1tqu, 1tqv, 1tqw, 2alw, 2f18, 2f1a, 2f1b, 2f7o, 2f7p, 2f7q, 2f7r, 3bub, 3bud, 3bui, 3bup Gene: alpha-Man-II, GmII (Drosophila melanogaster) Activity: Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase, with EC number 3.2.1.114 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Inhibition of Golgi alpha-mannosidase II (GMII), which acts late in the N-glycan processing pathway, provides a route to blocking cancer-induced changes in cell surface oligosaccharide structures. To probe the substrate requirements of GMII, oligosaccharides were synthesized that contained an alpha(1,3)- or alpha(1,6)-linked 1-thiomannoside. Surprisingly, these oligosaccharides were not observed in X-ray crystal structures of native Drosophila GMII (dGMII). However, a mutant enzyme in which the catalytic nucleophilic aspartate was changed to alanine (D204A) allowed visualization of soaked oligosaccharides and led to the identification of the binding site for the alpha(1,3)-linked mannoside of the natural substrate. These studies also indicate that the conformational change of the bound mannoside to a high-energy B 2,5 conformation is facilitated by steric hindrance from, and the formation of strong hydrogen bonds to, Asp204. The observation that 1-thio-linked mannosides are not well tolerated by the catalytic site of dGMII led to the synthesis of a pentasaccharide containing the alpha(1,6)-linked Man of the natural substrate and the beta(1,2)-linked GlcNAc moiety proposed to be accommodated by the extended binding site of the enzyme. A cocrystal structure of this compound with the D204A enzyme revealed the molecular interactions with the beta(1,2)-linked GlcNAc. The structure is consistent with the approximately 80-fold preference of dGMII for the cleavage of substrates containing a nonreducing beta(1,2)-linked GlcNAc. By contrast, the lysosomal mannosidase lacks an equivalent GlcNAc binding site and kinetic analysis indicates oligomannoside substrates without non-reducing-terminal GlcNAc modifications are preferred, suggesting that selective inhibitors for GMII could exploit the additional binding specificity of the GlcNAc binding site. Probing the Substrate Specificity of Golgi alpha-Mannosidase II by Use of Synthetic Oligosaccharides and a Catalytic Nucleophile Mutant.,Zhong W, Kuntz DA, Ember B, Singh H, Moremen KW, Rose DR, Boons GJ J Am Chem Soc. 2008 Jun 18;. PMID:18558690 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Mannosidase

spinqualitylabelsall models 3buq, resolution 2.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image