2OW6
Golgi alpha-mannosidase II complex with (1r,5s,6s,7r,8s)-1-thioniabicyclo[4.3.0]nonan-5,7,8-triol chloride
Summary for 2OW6
| Entry DOI | 10.2210/pdb2ow6/pdb |
| Related | 1HTY 1HWW 1HXK 1PS3 1QWN 1QWU 1QX1 1R33 1R34 1TQS 1TQT 1TQU 1TQV 1TQW 2ALW 2F18 2F1A 2F1B 2F7O 2F7Q 2F7R 2FYV 2OW7 |
| Descriptor | Alpha-mannosidase 2, 2-acetamido-2-deoxy-beta-D-glucopyranose, PHOSPHATE ION, ... (7 entities in total) |
| Functional Keywords | glycosyl hydrolase family 38, hydrolase |
| Biological source | Drosophila melanogaster (fruit fly) |
| Total number of polymer chains | 1 |
| Total formula weight | 120487.62 |
| Authors | Kuntz, D.A. (deposition date: 2007-02-15, release date: 2008-01-08, Last modification date: 2023-08-30) |
| Primary citation | Kumar, N.S.,Kuntz, D.A.,Wen, X.,Pinto, B.M.,Rose, D.R. Binding of sulfonium-ion analogues of di-epi-swainsonine and 8-epi-lentiginosine to Drosophila Golgi alpha-mannosidase II: The role of water in inhibitor binding. Proteins, 71:1484-1496, 2008 Cited by PubMed Abstract: Retaining glycosidases operate by a two-step catalytic mechanism in which the transition states are characterized by buildup of a partial positive charge at the anomeric center. Sulfonium-ion analogues of the naturally occurring glycosidase inhibitors, swainsonine and 8-epi-lentiginosine, in which the bridgehead nitrogen atom is replaced by a sulfonium-ion, were synthesized in order to test the hypothesis that a sulfonium salt carrying a permanent positive charge would be an effective glycosidase inhibitor. Initial prediction based on computational docking indicated three plausible binding modes to Drosophila Golgi alpha-mannosidase II (dGMII), the most likely being close to that of swainsonine. Observation of the binding of di-epi-thioswainsonine and 8-epi-thiolentiginosine to dGMII from crystallographic data, however, revealed an orientation different from swainsonine in the active site. Screening these two compounds against dGMII shows that they are inhibitors with IC(50) values of 2.0 and 0.014 mM, respectively. This dramatic difference in affinity between the two compounds, which differ by only one hydroxyl group, is rationalized in terms of bound water molecules and the water molecule substructure in the active site, as identified by comparison of high resolution X-ray crystal structures of several dGMII-inhibitor complexes. PubMed: 18076078DOI: 10.1002/prot.21850 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.19 Å) |
Structure validation
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