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PMID: 18669915 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

Conservation of peptide acceptor preferences between Drosophila and mammalian polypeptide-GalNAc transferase ortholog pairs.

Glycobiology ·Vol. 18 ·No. 11 ·2008-11-00 ·Pages 861-70

Gerken TA, Ten Hagen KG, Jamison O

Abstract

UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltrans- ferases (ppGalNAc Ts) comprise a large family of glycosyltransferases that initiate mucin-type protein O-glycosylation, transferring alpha-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 alpha-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.

MeSH Terms
Amino Acid Sequence Animals Binding Sites COS Cells Cattle Chlorocebus aethiops Drosophila/enzymology,metabolism Mammals Molecular Sequence Data N-Acetylgalactosaminyltransferases/chemistry,metabolism Peptide Fragments/chemistry,metabolism Sequence Alignment Substrate Specificity
Chemicals
Peptide Fragments N-Acetylgalactosaminyltransferases polypeptide N-acetylgalactosaminyltransferase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Gerken Thomas A
Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA. txg2@cwru.edu
Ten Hagen Kelly G
Jamison Oliver
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Article Info
Journal
Glycobiology
Abbr.
Glycobiology
ISSN
1460-2423
DOI
10.1093/glycob/cwn073
Email
txg2@cwru.edu
Published
2008-11-00
Epub
2008-00-31
Pages
861-70
Language
English
Region
England
NLM ID
9104124
PMCID
PMC2574660
Subset
IM
Grants
NCI NIH HHS · R01 CA078834 · United States
NCI NIH HHS · R01-CA-78834 · United States
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1093/glycob/cwn073 PMC Full Text View journal details
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