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PDBsum entry 3oay
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Immune system
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PDB id
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3oay
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Contents |
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* Residue conservation analysis
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PDB id:
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Immune system
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Title:
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A non-self sugar mimic of the HIV glycan shield shows enhanced antigenicity
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Structure:
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Fab 2g12, light chain. Chain: k, l. Engineered: yes. Fab 2g12, heavy chain. Chain: m, h. Engineered: yes
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Source:
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Homo sapiens. Organism_taxid: 9606. Organism_taxid: 9606
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Resolution:
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1.95Å
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R-factor:
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0.184
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R-free:
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0.223
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Authors:
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K.J.Doores,Z.Fulton,V.Hong,M.K.Patel,C.N.Scanlan,M.R.Wormald, M.G.Finn,D.R.Burton,I.A.Wilson,B.G.Davis
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Key ref:
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K.J.Doores
et al.
(2010).
A nonself sugar mimic of the HIV glycan shield shows enhanced antigenicity.
Proc Natl Acad Sci U S A,
107,
17107-17112.
PubMed id:
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Date:
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05-Aug-10
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Release date:
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12-Jan-11
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PROCHECK
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Headers
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References
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Proc Natl Acad Sci U S A
107:17107-17112
(2010)
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PubMed id:
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A nonself sugar mimic of the HIV glycan shield shows enhanced antigenicity.
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K.J.Doores,
Z.Fulton,
V.Hong,
M.K.Patel,
C.N.Scanlan,
M.R.Wormald,
M.G.Finn,
D.R.Burton,
I.A.Wilson,
B.G.Davis.
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ABSTRACT
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Antibody 2G12 uniquely neutralizes a broad range of HIV-1 isolates by binding
the high-mannose glycans on the HIV-1 surface glycoprotein, gp120. Antigens that
resemble these natural epitopes of 2G12 would be highly desirable components for
an HIV-1 vaccine. However, host-produced (self)-carbohydrate motifs have been
unsuccessful so far at eliciting 2G12-like antibodies that cross-react with
gp120. Based on the surprising observation that 2G12 binds nonproteinaceous
monosaccharide D-fructose with higher affinity than D-mannose, we show here that
a designed set of nonself, synthetic monosaccharides are potent antigens. When
introduced to the terminus of the D1 arm of protein glycans recognized by 2G12,
their antigenicity is significantly enhanced. Logical variation of these
unnatural sugars pinpointed key modifications, and the molecular basis of this
increased antigenicity was elucidated using high-resolution crystallographic
analyses. Virus-like particle protein conjugates containing such nonself glycans
are bound more tightly by 2G12. As immunogens they elicit higher titers of
antibodies than those immunogenic conjugates containing the self D1 glycan
motif. These antibodies generated from nonself immunogens also cross-react with
this self motif, which is found in the glycan shield, when it is presented in a
range of different conjugates and glycans. However, these antibodies did not
bind this glycan motif when present on gp120.
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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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M.C.Galan,
D.Benito-Alifonso,
and
G.M.Watt
(2011).
Carbohydrate chemistry in drug discovery.
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Org Biomol Chem,
9,
3598-3610.
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M.K.Patel,
B.Vijayakrishnan,
J.R.Koeppe,
J.M.Chalker,
K.J.Doores,
and
B.G.Davis
(2010).
Analysis of the dispersity in carbohydrate loading of synthetic glycoproteins using MALDI-TOF mass spectrometry.
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Chem Commun (Camb),
46,
9119-9121.
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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.
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Links
