Structure-based evolutionary relationship of glycosyltransferases: a case study of vertebrate β1,4-galactosyltransferase, invertebrate β1,4-N-acetylgalactosaminyltransferase and α-polypeptidyl-N-acetylgalactosaminyltransferase.
Cell surface glycans play important cellular functions and are synthesized by glycosyltransferases. Structure and function studies show that the donor sugar specificity of the invertebrate β1,4-N-acetyl-glactosaminyltransferase (β4GalNAc-T) and the vertebrate β1,4-galactosyltransferase I (β4Gal-T1) are related by a single amino acid residue change. Comparison of the catalytic domain crystal structures of the β4Gal-T1 and the α-polypeptidyl-GalNAc-T (αppGalNAc-T) shows that their protein structure and sequences are similar. Therefore, it seems that the invertebrate β4GalNAc-T and the catalytic domain of αppGalNAc-T might have emerged from a common primordial gene. When vertebrates emerged from invertebrates, the amino acid that determines the donor sugar specificity of the invertebrate β4GalNAc-T might have mutated, thus converting the enzyme to a β4Gal-T1 in vertebrates.
Ramakrishnan
Boopathy
B
Structural Glycobiology Section, Center for Cancer Research Nanobiology Program, NCI-Frederick, Frederick, MD 21702, USA.
Qasba
Pradman K
PK
D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D016695:Glycosyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007448:Invertebrates / Q000201:enzymology* / Q000235:genetics; D008969:Molecular Sequence Data; D017350:N-Acetylgalactosaminyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009237:N-Acetyllactosamine Synthase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014714:Vertebrates / Q000235:genetics; D000097763:Polypeptide N-acetylgalactosaminyltransferase
D016695:Glycosyltransferases; D017350:N-Acetylgalactosaminyltransferases; D009237:N-Acetyllactosamine Synthase; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C023220:(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase