3EJP
Golgi alpha-Mannosidase II in complex with 5-substituted swainsonine analog: (5R)-5-[2'-oxo-2'-(phenyl)ethyl]-swainsonine
Summary for 3EJP
| Entry DOI | 10.2210/pdb3ejp/pdb |
| Related | 1HTY 1HWW 1HXK 1PS2 1QWN 1R33 1R34 1TQV 2ALW 2F7O 2F7P 2F7Q 2F7R 2FYV 3BUB 3BUP 3CZN 3EJQ 3EJR 3EJS 3EJT 3EJU |
| Descriptor | Alpha-mannosidase 2, 2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (6 entities in total) |
| Functional Keywords | gh38 glycosidase, glycosidase, golgi apparatus, hydrolase, membrane, metal-binding, signal-anchor, transmembrane |
| Biological source | Drosophila melanogaster (Fruit fly) |
| Total number of polymer chains | 1 |
| Total formula weight | 120397.75 |
| Authors | Kuntz, D.A.,Rose, D.R. (deposition date: 2008-09-18, release date: 2009-10-13, Last modification date: 2023-08-30) |
| Primary citation | Kuntz, D.A.,Nakayama, S.,Shea, K.,Hori, H.,Uto, Y.,Nagasawa, H.,Rose, D.R. Structural Investigation of the Binding of 5-Substituted Swainsonine Analogues to Golgi alpha-Mannosidase II. Chembiochem, 11:673-680, 2010 Cited by PubMed Abstract: Golgi alpha-mannosidase II (GMII) is a key enzyme in the N-glycosylation pathway and is a potential target for cancer chemotherapy. The natural product swainsonine is a potent inhibitor of GMII. In this paper we characterize the binding of 5alpha-substituted swainsonine analogues to the soluble catalytic domain of Drosophila GMII by X-ray crystallography. These inhibitors enjoy an advantage over previously reported GMII inhibitors in that they did not significantly decrease the inhibitory potential of the swainsonine head-group. The phenyl groups of these analogues occupy a portion of the binding site not previously seen to be populated with either substrate analogues or other inhibitors and they form novel hydrophobic interactions. They displace a well-organized water cluster, but the presence of a C(10) carbonyl allows the reestablishment of important hydrogen bonds. Already approximately tenfold more active against the Golgi enzyme than the lysosomal enzyme, these inhibitors offer the potential of being extended into the N-acetylglucosamine binding site of GMII for the creation of even more potent and selective GMII inhibitors. PubMed: 20209559DOI: 10.1002/cbic.200900750 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.32 Å) |
Structure validation
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