Glycobiology Advance Access originally published online on July 31, 2008
Glycobiology 2008 18(11):861-870; doi:10.1093/glycob/cwn073
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Conservation of peptide acceptor preferences between Drosophila and mammalian polypeptide-GalNAc transferase ortholog pairs
2 Departments of Biochemistry and Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA
3 National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
4 Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA
1 To whom correspondence should be addressed: Tel: +1-216-368-4556; Fax: +1-216-368-4223; e-mail: txg2{at}cwru.edu
Received on May 23, 2008; revised on July 18, 2008; accepted on July 29, 2008
UDP-GalNAc:polypeptide 
-N-acetylgalactosaminyltrans- ferases (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 orthologs identifiable from mammals to single-cell organisms. The peptide substrate specificity and specific protein targets of the individual ppGalNAc T family members remain 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 TA, Raman J, Fritz TA, Jamison O. 2006. Identification of common and unique peptide substrate preferences for the UDP-GalNAc:polypeptide -N-acetylgalactosaminyltransferases T1 & T2 (ppGalNAc T1 & T2) derived from oriented random peptide substrates. J Biol Chem. 281:32403–32416). 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 orthologs of T1 and T2. The results from these studies suggest that the major peptide substrate determinants for these transferases are contained within 2 to 3 residues flanking the site of glycosylation. It is further found that the mammalian and fly T1 orthologs display very similar peptide substrate preferences, while the T2 orthologs 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 orthologs, 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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