Glycobiology Advance Access published online on July 31, 2008
Glycobiology, doi:10.1093/glycob/cwn073
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Conservation of peptide acceptor preferences between Drosophila and mammalian polypeptide-GalNAc transferase orthologue pairs
+ Depts. of Biochemistry and Pediatrics, Case Western Reserve Univ., Cleveland, OH 44106
* NIDCR, National Institutes of Health, Bethesda, MD 20892
Correspondence should be addressed to: Thomas A. Gerken: Dept. of Pediatrics and Biochemistry, Case Western Reserve University School of Medicine BRB, 2109 Adelbert Rd. Cleveland OH 44106-4948. Tel.: 216-368-4556; Fax: 216-368-4223; E-mail: txg2{at}cwru.edu
Received on May 23, 2008; accepted on July 29, 2008
UDP-GalNAc: polypeptide 
-N-acetylgalactosaminyltransferases (ppGalNAc Ts) comprise a large family of glycosyltransferases that initiate mucin-type protein O-glycosylation, transferring -GalNAc to Thr and Ser residues of polypeptide acceptors. Families of ppGalNAc Ts are found across diverse eukaryotes with orthologues identifiable from mammals to single cell organisms. The peptide substrate specificity and specific protein targets of the individual ppGalNAc T family members remains poorly understood. Previously, we reported a series of oriented random peptide substrate libraries for quantitatively determining the peptide substrate specificities of the mammalian ppGalNAc T1 and T2 (Gerken et al, J. Biol. Chem. (2006)). With these substrates, previously unknown features of the transferases were revealed. Utilizing these and a new lengthened set of random peptides, studies have now been performed on PGANT5 and PGANT2, the Drosophila orthologues of T1 and T2. The results from these studies suggests that the major peptide substrate determinants for these transferases is contained within 2 to 3 residues flanking the site of glycosylation. It is further found that the mammalian and fly T1 orthologues display very similar peptide substrate preferences, while the T2 orthologues are nearly indistinguishable, suggesting similar peptide preferences amongst orthologous pairs have been maintained across evolution. This conclusion is further supported by sequence homology comparisons of each of the transferase orthologues, showing that the peptide substrate and UDP binding site residues are more highly conserved between species relative to their remaining catalytic and lectin domain residues.
Key words: evolution / mucin / O-glycosylation / sequence motifs / UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase
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