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PDBsum entry 3ddf
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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 mannosidase ii complex with (3r,4r,5r)-3,4-dihydroxy-5-({[(1r)- 2-hydroxy-1 phenylethyl]amino}methyl) pyrrolidin-2-one
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Structure:
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Alpha-mannosidase 2. Chain: a. Fragment: catalytic domain. Synonym: alpha-mannosidase ii. Mannosyl-oligosaccharide 1,3-1,6- alpha-mannosidase. Man ii. Golgi alpha-mannosidase ii. Aman 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. Expression_system_cell_line: s2 cells.
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Resolution:
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1.20Å
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R-factor:
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0.115
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R-free:
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0.151
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Authors:
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D.A.Kuntz,D.R.Rose,D.Hoffman
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Key ref:
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H.Fiaux
et al.
(2008).
Functionalized pyrrolidine inhibitors of human type II alpha-mannosidases as anti-cancer agents: optimizing the fit to the active site.
Bioorg Med Chem Lett,
16,
7337-7346.
PubMed id:
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Date:
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05-Jun-08
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Release date:
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01-Jul-08
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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.
1015 a.a.*
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Key: |
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PfamA domain |
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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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Bioorg Med Chem Lett
16:7337-7346
(2008)
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PubMed id:
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Functionalized pyrrolidine inhibitors of human type II alpha-mannosidases as anti-cancer agents: optimizing the fit to the active site.
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H.Fiaux,
D.A.Kuntz,
D.Hoffman,
R.C.Janzer,
S.Gerber-Lemaire,
D.R.Rose,
L.Juillerat-Jeanneret.
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ABSTRACT
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Refining the chemical structure of functionalized pyrrolidine-based inhibitors
of Golgi alpha-mannosidase II (GMII) to optimize binding affinity provided a
lead molecule that demonstrated nanomolar competitive inhibition of
alpha-mannosidases II and an optimal fit in the active site of Drosophila GMII
by X-ray crystallography. Esters of this lead compound also inhibited the growth
of human glioblastoma and brain-derived endothelial cells more than the growth
of non-tumoral human fibroblasts, suggesting their potential for anti-cancer
therapy.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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D.A.Kuntz,
S.Nakayama,
K.Shea,
H.Hori,
Y.Uto,
H.Nagasawa,
and
D.R.Rose
(2010).
Structural investigation of the binding of 5-substituted swainsonine analogues to Golgi alpha-mannosidase II.
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Chembiochem,
11,
673-680.
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PDB codes:
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D.J.Coleman,
D.A.Kuntz,
M.Venkatesan,
G.M.Cook,
S.P.Williamson,
D.R.Rose,
and
J.J.Naleway
(2010).
A long-wavelength fluorescent substrate for continuous fluorometric determination of alpha-mannosidase activity: resorufin alpha-D-mannopyranoside.
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Anal Biochem,
399,
7.
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M.D.Suits,
Y.Zhu,
E.J.Taylor,
J.Walton,
D.L.Zechel,
H.J.Gilbert,
and
G.J.Davies
(2010).
Structure and kinetic investigation of Streptococcus pyogenes family GH38 alpha-mannosidase.
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PLoS One,
5,
e9006.
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PDB codes:
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D.A.Kuntz,
W.Zhong,
J.Guo,
D.R.Rose,
and
G.J.Boons
(2009).
The Molecular Basis of Inhibition of Golgi alpha-Mannosidase II by Mannostatin A.
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Chembiochem,
10,
268-277.
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PDB codes:
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M.Venkatesan,
D.A.Kuntz,
and
D.R.Rose
(2009).
Human lysosomal alpha-mannosidases exhibit different inhibition and metal binding properties.
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Protein Sci,
18,
2242-2251.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
