Thursday, October 30, 2008

Protein of the month

Every month protein spotlight from Expasy highlights a protein.The archive can be found here.
This month is the month for 2 proteins that has ability to make blood group A, B, AB to universal donor blood groups. There are in fact 2 molecules one for blood group A and one for blood group B. These are 2 bacterial glycosidases – α-N-acetylgalactosaminidase and α-1,3-galactosidase A.

As the blood groups are identified by the presence of an antigen on its surface that makes it either A, B or AB. The O group does not have any known antigen. This particular antigen is determined by a carbohydrate structure on the end of oligosaccharide chains on glycoproteins and glycolipids lodged in the cell’s membrane. Blood group A is defined by a terminal α-1,3-linked N-acetylgalactosamine (GalNAc). Blood group B is defined by a terminal α-1,3-linked galactose (Gal). And blood group O (which should really be pronounced ‘zero’) lacks both of these monosaccharides but instead is defined by an α-1,2-linked fucose. If there was a way of wiping off the monosaccharide entities (GalNAc and Gal) on A cells and B cells respectively, then blood groups A and B could be converted into the universal blood group O. What scientists then needed to find was something very small which could snap off the monosaccharide tips: an enzyme of some sort.

α-N-acetylgalactosaminidase and α-1,3-galactosidase A – which have the power to cleave and discard the GalNAc and Gal entities thus converting a red blood cell into a cell with neither a recognisable A nor B blood group antigen. In other words, they can convert A and B blood groups into a universal O blood group. Alpha-N-acetylgalactosaminidase is known in greater molecular detail than its homolog α-1,3-galactosidase A. Surprisingly, unlike other glycosidases of the same family, it needs the help of a cofactor (NAD+), which is nestled in the depths of a narrow tunnel, to cleave the GalNAc monosaccharide. Another part of the enzyme forms a crater which is large enough to accommodate an antigen from which the monosaccharide tip can be cleaved.

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