2g5r: Difference between revisions
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[[Image:2g5r.gif|left|200px]] | [[Image:2g5r.gif|left|200px]] | ||
'''Crystal structure of Siglec-7 in complex with methyl-9-(aminooxalyl-amino)-9-deoxyNeu5Ac (oxamido-Neu5Ac)''' | {{Structure | ||
|PDB= 2g5r |SIZE=350|CAPTION= <scene name='initialview01'>2g5r</scene>, resolution 1.600Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NXD:METHYL+5-(ACETYLAMINO)-9-{[AMINO(OXO)ACETYL]AMINO}-3,5,9-TRIDEOXY-D-GLYCERO-ALPHA-D-GLUCO-NON-2-ULOPYRANOSIDONIC+ACID'>NXD</scene> and <scene name='pdbligand=CYS:CYSTEINE'>CYS</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''Crystal structure of Siglec-7 in complex with methyl-9-(aminooxalyl-amino)-9-deoxyNeu5Ac (oxamido-Neu5Ac)''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2G5R is a [ | 2G5R is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G5R OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/16623661 16623661] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: siglec]] | [[Category: siglec]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:00:44 2008'' | ||
Revision as of 18:00, 20 March 2008
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| , resolution 1.600Å | |||||||
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of Siglec-7 in complex with methyl-9-(aminooxalyl-amino)-9-deoxyNeu5Ac (oxamido-Neu5Ac)
OverviewOverview
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.
About this StructureAbout this Structure
2G5R is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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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