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PDBsum entry 3ejs
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Contents |
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* Residue conservation analysis
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PDB id:
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Hydrolase
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Title:
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Golgi alpha-mannosidase ii in complex with 5-substituted swainsonine analog: (5s)-5-[2'-(4-tert-butylphenyl)ethyl]-swainsonine
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Structure:
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Alpha-mannosidase 2. Chain: a. Fragment: catalytic domain. Unp residues 76-1108. Synonym: alpha-mannosidase ii, aman ii, man ii, mannosyl- oligosaccharide 1,3-1,6-alpha-mannosidase, golgi alpha-mannosidase ii. Engineered: yes
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Source:
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Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: alpha-man-ii, gmii. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227.
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Resolution:
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1.35Å
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R-factor:
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0.191
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R-free:
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0.213
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Authors:
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D.A.Kuntz,K.Shea,D.R.Rose
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Key ref:
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D.A.Kuntz
et al.
(2010).
Structural investigation of the binding of 5-substituted swainsonine analogues to Golgi alpha-mannosidase II.
Chembiochem,
11,
673-680.
PubMed id:
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Date:
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18-Sep-08
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Release date:
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13-Oct-09
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PROCHECK
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Headers
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References
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Q24451
(MAN2_DROME) -
Alpha-mannosidase 2 from Drosophila melanogaster
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Seq:
Struc:
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1108 a.a.
1016 a.a.*
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Key: |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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Enzyme class:
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E.C.3.2.1.114
- mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase.
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Pathway:
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Mannosyl-glycoprotein N-acetylglucosaminyltransferases
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Reaction:
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N4-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->3)-[alpha- D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)- beta-D-GlcNAc}-L-asparaginyl-[protein] + 2 H2O = 2 alpha-D-mannopyranose + an N4-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]- beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-L-asparaginyl- [protein]
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Chembiochem
11:673-680
(2010)
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PubMed id:
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Structural investigation of the binding of 5-substituted swainsonine analogues to Golgi alpha-mannosidase II.
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D.A.Kuntz,
S.Nakayama,
K.Shea,
H.Hori,
Y.Uto,
H.Nagasawa,
D.R.Rose.
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ABSTRACT
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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.
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Links
