Abstract
Siglecs are attractive therapeutic target of the major homologous subfamily of I-type lectins. The primary role of Siglecs may actually lie in the recognition and phagocytosis of bacterial pathogens that express sialic acids, maintenance of myelin organization, and inhibition of neurite outgrowth, cell-cell interactions between neurons and glial cells etc. Siglec-2, a member of the Siglec family expressed on the surface of maturing B cells and B cell lymphomas and regulates signal transduction. In this work, 3-D structure of human Siglec-2 was predicted using molecular modeling techniques. The structure of the complex in solution of Siglec-2 with ligand, 6′-Sialyl-N-acetyl lactose (6′-SialylLacNAc) was predicted using a novel docking technique. The structural analysis of the complex and calculation of theoretical dissociation constant value will help to ascertain functional roles of such sugar binding protein.
Highlights
The Siglecs are a specialized subgroup of the Ig super family that can recognize sialylated glycoconjugates (Crocker et al, 1998)
Siglecs can be divided into two subgroups: Sialoadhesin (Siglec-1), Siglec-2 (CD22), MAG (Siglec-4) and Siglec-15 constitute one subgroup, share ~25– 30% sequence identity in the extracellular region, and have divergent cytoplasmic tails and the second subgroup consists of the CD33-related Siglecs
I have modeled the 3-D structure of human
Summary
The Siglecs are a specialized subgroup of the Ig super family that can recognize sialylated glycoconjugates (Crocker et al, 1998). Siglecs are type 1 membrane proteins, recognizes sialylated glycoconjugates by an N-terminal sialic acidbinding V-set Ig domain which followed by a transmembrane domain, and a cytoplasmic tail and variable number of C2-set Ig-like domains (Angata et al, 2001). Siglecs can be divided into two subgroups: Sialoadhesin (Siglec-1), Siglec-2 (CD22), MAG (Siglec-4) and Siglec-15 constitute one subgroup, share ~25– 30% sequence identity in the extracellular region, and have divergent cytoplasmic tails and the second subgroup consists of the CD33-related Siglecs. They share 50–80% sequence similarity and have in their cytoplasmic tails two highly conserved tyrosine-based motifs. Expression of each human Siglec in a cell type-specific fashion, mainly in the hematopoietic and immune systems of humans, suggesting involvement in discrete functions ranging from regulation of neuronal cell growth and maintenance of myelination in the nervous system (MAG) (Li et al, 1994; Montag et al, 1994) and control of myeloid cell interactions (sialoadhesin) (Crocker et al, 1997) and CD33 (Freeman et al, 1995) to activation of B cells
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