FOLD RECOGNITION AND MOLECULAR MODELING OF A LECTIN-LIKE DOMAIN IN UDP-GALNAC - POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASES

By use of threading methods, the C-terminal region of uridine diphosph o-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransfera ses (ppGalNAc-transferases) was predicted to have the same fold as the lectin-domain of the plant cytotoxins ricin and abrin-a, for which cr ystal structure are available. The sequence are very low. Nevertheless , the amino acids in the hydrophobic core essential for the structure stability and the cysteine residues are conserved. In addition, the am ino-acids involved in carbohydrate binding are conserved in ppGalNAc-t ransferases. The extra C-terminal domain of these enzymes is therefore a putative glycan-binding domain. A model of the lectinlike domain of human ppGalNAc-transferase T1 was built using knowledge based methods . Geometry optimization of the complex with galactose allowed predicti on that this domain could bind this monosaccharide. However, the inter action seems to be rather weak, and at the moment there is no evidence that ppGalNAc-transferases displays a lectin activity in vivo.