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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 mannostatin analo 3s,4r,5r)-5-aminocyclopentane-1,2,3,4-tetraol
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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-mann ii. Engineered: yes
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Source:
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Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: alpha-man-ii, gmii, cg18802. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227.
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Resolution:
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1.42Å
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R-factor:
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0.149
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R-free:
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0.174
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Authors:
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D.A.Kuntz,D.R.Rose
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Key ref:
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D.A.Kuntz
et al.
(2009).
The molecular basis of inhibition of Golgi alpha-mannosidase II by mannostatin A.
Chembiochem,
10,
268-277.
PubMed id:
DOI:
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Date:
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23-Jul-08
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Release date:
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07-Jul-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
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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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Gene Ontology (GO) functional annotation
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Cellular component
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membrane
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6 terms
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Biological process
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metabolic process
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3 terms
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Biochemical function
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catalytic activity
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11 terms
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DOI no:
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Chembiochem
10:268-277
(2009)
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PubMed id:
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The molecular basis of inhibition of Golgi alpha-mannosidase II by mannostatin A.
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D.A.Kuntz,
W.Zhong,
J.Guo,
D.R.Rose,
G.J.Boons.
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ABSTRACT
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Mannostatin A is a potent inhibitor of the mannose-trimming enzyme, Golgi
alpha-mannosidase II (GMII), which acts late in the N-glycan processing pathway.
Inhibition of this enzyme provides a route to blocking the
transformation-associated changes in cancer cell surface oligosaccharide
structures. Here, we report on the synthesis of new Mannostatin derivatives and
analyze their binding in the active site of Drosophila GMII by X-ray
crystallography. The results indicate that the interaction with the backbone
carbonyl of Arg876 is crucial to the high potency of the inhibitor-an effect
enhanced by the hydrophobic interaction between the thiomethyl group and an
aromatic pocket vicinal to the cleavage site. The various structures indicate
that differences in the hydration of protein-ligand complexes are also important
determinants of plasticity as well as selectivity of inhibitor binding.
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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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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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Y.Zhu,
M.D.Suits,
A.J.Thompson,
S.Chavan,
Z.Dinev,
C.Dumon,
N.Smith,
K.W.Moremen,
Y.Xiang,
A.Siriwardena,
S.J.Williams,
H.J.Gilbert,
and
G.J.Davies
(2010).
Mechanistic insights into a Ca2+-dependent family of alpha-mannosidases in a human gut symbiont.
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Nat Chem Biol, 6,
125-132.
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PDB codes:
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J.Calveras,
M.Egido-Gabás,
L.Gómez,
J.Casas,
T.Parella,
J.Joglar,
J.Bujons,
and
P.Clapés
(2009).
Dihydroxyacetone phosphate aldolase catalyzed synthesis of structurally diverse polyhydroxylated pyrrolidine derivatives and evaluation of their glycosidase inhibitory properties.
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Chemistry, 15,
7310-7328.
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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
