This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Carbohydrate ligands that bind to isolectins from the African legume Griffonia simplicifolia (GS) and the peptides that mimic these ligands were selected to study carbohydrate mimicry by synthetic peptides. The GS1 family of glycoproteins is composed of five tetrameric isolectins resulting from a combination of two different glycoprotein subunits, A and B. The A subunit has strong affinity for terminal N-acetyl-D-galactosamine groups but also reacts with terminal alpha-galactosyl residues. The B subunit is selective for terminal alpha-D-galactosyl residues. 1A4 and 1B4 were purified from the legume source. The three dimensional X-ray crystal structures of 1B4 bound to the xenoantigen Gal-alpha-(1,3)Gal, and 1A4 bound to blood group A trisaccharide GalNAc-alpha-(1,3)-[Fuc-alpha-(1,2)]-Gal, have been previously determined by our group. We are currently studying the binding of the synthetic peptide mimics DAHWESWL and SSLRGF to 1B4 and 1A4. Polyporus squamosus agglutinin (PSA) from mushroom Polyporus squamosus is a 28 kDa lectin which agglutinates human A, B, and O and rabbit red blood cells. It binds beta-D-galactosides and exhibits high specificity and affinity towards nonreducing terminal Neu5Ac-alpha-(2,6)-Gal-beta-(1,4)-Glc/GlcNac (6-sialylated type II chain) of N-glycans. The strict specificity of PSA for alpha-(2,6) linked sialic acid residues makes it a valuable tool in biomedical and glycobiological studies. The structure of PSA and its binding interaction with its ligand is unknown. PSA shares very low sequence homology with known protein structures. Native PSA crystals were grown with the ligand 6-sialyllactosamine and X-ray data were collected at 1.7 resolution. Derivative heavy atom crystals of PSA are being grown to help solve the crystal structure of PSA. To obtain more information about the carbohydrate recognition domain of PSA, a truncated, active, C-terminal deletion mutant (PSA-D1) has been constructed.
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