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2df3

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{{STRUCTURE_2df3| PDB=2df3 | SCENE= }}
{{STRUCTURE_2df3| PDB=2df3 | SCENE= }}
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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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===The structure of Siglec-7 in complex with alpha(2,3)/alpha(2,6) disialyl lactotetraosyl 2-(trimethylsilyl)ethyl===
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==Overview==
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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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{{ABSTRACT_PUBMED_16623661}}
==About this Structure==
==About this Structure==
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[[Category: Sialic acid]]
[[Category: Sialic acid]]
[[Category: Siglec]]
[[Category: Siglec]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 00:18:10 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:30:42 2008''

Revision as of 11:30, 28 July 2008

Image:2df3.png

Template:STRUCTURE 2df3

The structure of Siglec-7 in complex with alpha(2,3)/alpha(2,6) disialyl lactotetraosyl 2-(trimethylsilyl)ethyl

Template:ABSTRACT PUBMED 16623661

About this Structure

2DF3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The structure of siglec-7 in complex with sialosides: leads for rational structure-based inhibitor design., Attrill H, Takazawa H, Witt S, Kelm S, Isecke R, Brossmer R, Ando T, Ishida H, Kiso M, Crocker PR, van Aalten DM, Biochem J. 2006 Jul 15;397(2):271-8. PMID:16623661

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