PMID: 23999306

 

    Legend: Gene, Sites

Title : The structure of human α-2,6-sialyltransferase reveals the binding mode of complex glycans

Abstract :
  1. Human β-galactoside α-2,6-sialyltransferase I (ST6Gal-I) establishes the final glycosylation pattern of many glycoproteins by transferring a sialyl moiety to a terminal galactose
  2. Complete sialylation of therapeutic immunoglobulins is essential for their anti-inflammatory activity and protein stability, but is difficult to achieve in vitro owing to the limited activity of ST6Gal-I towards some galactose acceptors
  3. No structural information on ST6Gal-I that could help to improve the enzymatic properties of ST6Gal-I for biotechnological purposes is currently available
  4. Here, the crystal structures of human ST6Gal-I in complex with the product cytidine 5'-monophosphate and in complex with cytidine and phosphate are described
  5. These complexes allow the rationalization of the inhibitory activity of cytosine-based nucleotides
  6. ST6Gal-I adopts a variant of the canonical glycosyltransferase A fold and differs from related sialyltransferases by several large insertions and deletions that determine its regiospecificity and substrate specificity
  7. A large glycan from a symmetry mate localizes to the active site of ST6Gal-I in an orientation compatible with catalysis
  8. The glycan binding mode can be generalized to any glycoprotein that is a substrate of ST6Gal-I
  9. Comparison with a bacterial sialyltransferase in complex with a modified sialyl donor lends insight into the Michaelis complex
  10. The results support an SN2 mechanism with inversion of configuration at the sialyl residue and suggest substrate-assisted catalysis with a charge-relay mechanism that bears a conceptual similarity to serine proteases
Output (sent_index, trigger, protein, sugar, site):
  • 1. glycoproteins, , glycoproteins, -, -
  • 1. glycosylation, , glycoproteins, -, -
  • 1. α-2,6-sialyltransferase, , α-2,6-sialyltransferase I, ST6Gal-I, -
  • 2. sialylation, , protein, -, -
  • 8. glycoprotein, , glycoprotein, -, -
Output(Part-Of) (sent_index, protein, site):
*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

 

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