Role of a single amino acid in the evolution of glycans of invertebrates and vertebrates

Structures of glycoconjugate N-glycans and glycolipids of invertebrates show significant differences from those of vertebrates. These differences are due largely to the vertebrate beta 1,4-galactosyltransferase-1 (beta 4Gal-T1), which is found as a 1,4-N-acetylgalactosaminyltransferase (beta 4GalNAc-T1) in invertebrates. Mutation of Tyr285 to Ile or Leu in human beta 4Gal-T1 converts the enzyme into an equally efficient 4GaINAc-Tl. A comparison of all the human beta 4Gal-T1 ortholog enzymes shows that this Tyr285 residue in human beta 4Gal-T1 is conserved either as Tyr or Phe in all vertebrate enzymes, invertebrate enzymes conserved an Ile Leu. We find mutation corresponding residue beta 4GlNAc-T1 converts the enzyme to a beta 4Gal-T1 by reducing its N-acetylgalactosaminyltransferase activity by nearly 1000-fold, while enhancing its galactosyltransferase activity by 80-fold. Furthermore, we find that, similar to the vertebrate/mammalian beta 4Gal-T1 enzymes, the wild-type Drosophila beta 4GalNAc-T1 enzyme binds to a mammary gland-specific protein, alpha-lactalbumin (alpha-LA). Thus, it would seem that, during the evolution of vertebrates from invertebrates over 500 million years ago, beta 4Gal-T1 appeared as a result of the single amino acid substitution of Tyr or Phe for Leu or Ile in the invertebrate beta 4GalNAc-T1. Subsequently, the preexisting alpha-LA-binding site was utilized during mammalian evolution to synthesize lactose in the mammary gland during lactation. (c) 2006 Published by Elsevier Ltd.

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