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PDBsum entry 2df3
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Cell adhesion
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PDB id
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2df3
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Contents |
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* Residue conservation analysis
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PDB id:
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| Name: |
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Cell adhesion
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Title:
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The structure of siglec-7 in complex with alpha(2,3)/alpha(2,6) disialyl lactotetraosyl 2-(trimethylsilyl)ethyl
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Structure:
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Sialic acid-binding ig-like lectin 7. Chain: a. Fragment: ig-like v-type. Synonym: siglec-7,adhesion inhibitory receptor molecule 1,airm-1, cdw328,d-siglec,qa79 membrane protein,p75. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: siglec7, airm1. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell_line: cho lec1.
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Resolution:
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1.90Å
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R-factor:
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0.197
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R-free:
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0.237
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Authors:
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H.Attrill
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Key ref:
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H.Attrill
et al.
(2006).
The structure of siglec-7 in complex with sialosides: leads for rational structure-based inhibitor design.
Biochem J,
397,
271-278.
PubMed id:
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Date:
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23-Feb-06
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Release date:
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20-Jun-06
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PROCHECK
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Headers
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References
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Q9Y286
(SIGL7_HUMAN) -
Sialic acid-binding Ig-like lectin 7 from Homo sapiens
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Seq:
Struc:
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467 a.a.
114 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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Biochem J
397:271-278
(2006)
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PubMed id:
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The structure of siglec-7 in complex with sialosides: leads for rational structure-based inhibitor design.
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H.Attrill,
H.Takazawa,
S.Witt,
S.Kelm,
R.Isecke,
R.Brossmer,
T.Ando,
H.Ishida,
M.Kiso,
P.R.Crocker,
D.M.van Aalten.
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ABSTRACT
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Siglecs (sialic acid binding Ig-like lectins) are transmembrane receptors for
sialylated glycoconjugates that modulate cellular interactions and signalling
events in the haematopoietic, immune and nervous systems. Siglec-7 is a
structural prototype for the recently described family of immune inhibitory
CD33-related siglecs and is predominantly expressed on natural killer cells and
monocytes, as well as subsets of CD8 T-cells. Siglec-specific inhibitors are
desired for the detection of masked and unmasked forms of siglecs, to aid in
dissection of signalling pathways and as tools to investigate siglecs as
potential therapeutic targets. As a first step towards this end, we present the
crystal structure of siglec-7 in complex with a sialylated ligand, the
ganglioside analogue DSLc4 [alpha(2,3)/alpha(2,6) disialyl lactotetraosyl
2-(trimethylsilyl)ethyl], which allows for a detailed description of the binding
site, required for structure-guided inhibitor design. Mutagenesis and binding
assays were used to demonstrate a key structural role for Lys131, a residue that
changes conformation upon sialic acid binding. Differences between the binding
sites of siglec family members were then exploited using alpha-methyl Neu5Ac
(N-acetylneuraminic acid) as a basic scaffold. A co-crystal of siglec-7 in
complex with the sialoside inhibitor, oxamido-Neu5Ac [methyl
alpha-9-(amino-oxalyl-amino)-9-deoxy-Neu5Ac] and inhibition data for the
sialosides gives clear leads for future inhibitor design.
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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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Y.Akune,
M.Hosoda,
S.Kaiya,
D.Shinmachi,
and
K.F.Aoki-Kinoshita
(2010).
The RINGS resource for glycome informatics analysis and data mining on the Web.
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OMICS,
14,
475-486.
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M.A.Zhuravleva,
K.Trandem,
and
P.D.Sun
(2008).
Structural implications of Siglec-5-mediated sialoglycan recognition.
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J Mol Biol,
375,
437-447.
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PDB codes:
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M.von Itzstein
(2008).
Disease-associated carbohydrate-recognising proteins and structure-based inhibitor design.
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Curr Opin Struct Biol,
18,
558-566.
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D.A.Patel,
J.E.Henry,
and
T.A.Good
(2007).
Attenuation of beta-amyloid-induced toxicity by sialic-acid-conjugated dendrimers: role of sialic acid attachment.
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Brain Res,
1161,
95.
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P.R.Crocker,
J.C.Paulson,
and
A.Varki
(2007).
Siglecs and their roles in the immune system.
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Nat Rev Immunol,
7,
255-266.
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Y.Liu,
T.Feizi,
M.A.Campanero-Rhodes,
R.A.Childs,
Y.Zhang,
B.Mulloy,
P.G.Evans,
H.M.Osborn,
D.Otto,
P.R.Crocker,
and
W.Chai
(2007).
Neoglycolipid probes prepared via oxime ligation for microarray analysis of oligosaccharide-protein interactions.
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Chem Biol,
14,
847-859.
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H.Attrill,
A.Imamura,
R.S.Sharma,
M.Kiso,
P.R.Crocker,
and
D.M.van Aalten
(2006).
Siglec-7 undergoes a major conformational change when complexed with the alpha(2,8)-disialylganglioside GT1b.
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J Biol Chem,
281,
32774-32783.
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PDB code:
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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
