| Structural highlights
3eju 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, 1r33, 1r34, 1tqv, 2alw, 2f7o, 2f7p, 2f7q, 2f7r, 2fyv, 3bub, 3bup, 3czn, 3ejp, 3ejq, 3ejr, 3ejs, 3ejt |
| 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 |
Function
[MAN2_DROME] Catalyzes the first committed step in the biosynthesis of complex N-glycans. It controls conversion of high mannose to complex N-glycans; the final hydrolytic step in the N-glycan maturation pathway (By similarity).
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
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.
Structural Investigation of the Binding of 5-Substituted Swainsonine Analogues to Golgi alpha-Mannosidase II.,Kuntz DA, Nakayama S, Shea K, Hori H, Uto Y, Nagasawa H, Rose DR Chembiochem. 2010 Mar 5;11(5):673-680. PMID:20209559[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kuntz DA, Nakayama S, Shea K, Hori H, Uto Y, Nagasawa H, Rose DR. Structural Investigation of the Binding of 5-Substituted Swainsonine Analogues to Golgi alpha-Mannosidase II. Chembiochem. 2010 Mar 5;11(5):673-680. PMID:20209559 doi:10.1002/cbic.200900750
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