N-glycosyltransferase

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Glycosyl transferase family 41
Identifiers
SymbolGT41
PfamPF13844
CAZyGT41
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

N-glycosyltransferase is an

amino acid sequence asparagine—-any amino acid except proline—serine or threonine
(N–x–S/T), with some variations.

Such enzymes have been found in the bacteria Actinobacillus pleuropneumoniae (whose N-glycosyltransferase is the best researched member of this enzyme family) and Haemophilus influenzae, and later in other bacterial species such as Escherichia coli. N-glycosyltransferases usually target adhesin proteins, which are involved in the attachment of bacterial cells to epithelia (in pathogenic bacteria); glycosylation is important for the stability and function of the adhesins.

History and definition

N-glycosyltransferase activity was first discovered in 2003 by St. Geme et al. in

eukaryotic process[5] before such processes were discovered in prokaryotes, including N-glycosyltransferases.[3]

Biochemistry

N-glycosyltransferases are an unusual

nucleophilic attack on the sugar substrate.[8]

N-glycosyltransferases from

hydrolyze sugar-nucleotides in the absence of a substrate,[17] a pattern frequently observed in glycosyltransferases,[18] and some N-glycosyltransferases can attach additional hexoses on oxygen atoms of the protein-linked hexose.[7] N-glycosylation by Actinobacillus pleuropneumoniae HMW1C does not require metals,[12] consistent with observations made on other GT41 family glycosyltransferases[19] and a distinction from oligosaccharyltransferases.[12]

Classification

Structurally N-glycosyltransferases belong to the GT41 family of glycosyltransferases and resemble

cytosolic targets.[8] Regular N-linked oligosaccharyltransferases belong to a different protein family, STT3.[20] The Haemophilus influenzae N-glycosyltransferase has domains with homologies to glutathione S-transferase and glycogen synthase.[21]

The N-glycosyltransferases are subdivided into two functional classes, the first (e.g several Yersinia, Escherichia coli and Burkholderia sp.) is linked to trimeric autotransporter adhesins and the second has enzymes genomically linked to ribosome and carbohydrate metabolism associated proteins (e.g Actinobacillus pleuropneumoniae, Haemophilus ducreyi and Kingella kingae).[22]

Functions

N-linked glycosylation is an important process, especially in eukaryotes where over half of all proteins have N-linked sugars attached[13] and where it is the most common form of glycosylation.[23] The processes are also important in prokaryotes[13] and archaeans.[24] In animals for example protein processing in the endoplasmic reticulum and several functions of the immune system are dependent on glycosylation.[9][b]

The principal substrates of N-glycosyltransferases are

pathogenic gammaproteobacteria,[28] such as Yersinia and other pasteurellaceae.[8] These homologues are very similar to the Actinobacillus pleuropneumoniae enzyme and can glycosylate the Haemophilus influenzae HMW1A adhesin.[29]

N-glycosyltransferases may be a novel glycoengineering tool,[30] considering that they do not require a lipid carrier to perform their function.[31] Glycosylation is important for the function of many proteins and the production of glycosylated proteins can be a challenge.[26] Potential uses of glycoengineering tools include the creation of vaccines against protein-bound polysaccharides.[32]

Examples

  • N-acetylglucosamine.[17] Its structure and the sites involved in substrate binding have been elucidated.[40] The N-glycosyltransferase is accompanied by another glycosyltransferase which attaches glucose to a protein-bound glycan,[41] and the two glycosyltransferases are part of an operon together with a third protein that is involved in the methylthiolation of ribosomes.[42]
  • epithelia.[44]
  • In Haemophilus influenzae (a respiratory tract pathogen[7]), the N-glycosyltransferase HMW1C attaches galactose and glucose taken from a nucleotide carrier to the HMW1A adhesin. The process is important for the stability of the HMW1A protein. Notably, HMW1C uses the N–X–S/T sequon as a substrate, the same sequon targeted by oligosaccharyltransferase,[13] and can also attach additional hexoses to an already protein-bound hexose.[45] The sugars are attached to an UDP carrier,[24][8] the enzyme itself is cytoplasmic and transfers 47 hexoses on to its substrate HMW1A,[24][23] although not all candidate sequons are targeted.[31] It resembles O-glycosyltransferases in some aspects more than N-glycosylating enzymes,[46] and is very similar to the Actinobacillus pleuropneumoniae enzyme.[31] Structurally, it features a GT-B fold with two subdomains that resemble a Rossmann fold and an AAD domain.[45] There is evidence that amino acid sequences containing the sequon are selected against in Haemophilus influenzae proteins, probably because the N-glycosyltransferase is not target specific and the presence of sequons would result in harmful glycosylation of off-target proteins.[47] Haemophilus influenzae has an additional HMW1C homologue HMW2C,[48] which together with the adhesin HMW2 forms a similar substrate-enzyme system.[45] The genomic locus of HMW1C is right next to the locus of HMW1A.[49]
  • orthologous to HMW1A of Haemophilus influenzae.[50] EtpA operates as an adhesin that mediates the binding to intestinal epithelia[6] and failure of glycosylation changes the adherence behaviour of the bacteria.[22]
  • epithelia;[51] in its absence adhesion and the expression of the Knh protein are impaired.[44] The glycosylation process in Kingella kingae is not strictly bound to the consensus sequon.[52]
  • Yersinia enterocolitica has a functional N-glycosyltransferase.[20][8] It also has a protein similar to HMW1C, but it is not known if it has the same activity.[50]
  • Other homologues have been found in Bibersteinia trehalosi,[14] Burkholderia species, Escherichia coli, Haemophilus ducreyi, Mannheimia species, Xanthomonas species, Yersinia pestis and Yersinia pseudotuberculosis.[6][1]

Notes

  1. ^ Regular N-glycosyltransferases are oligosaccharide-transferring enzymes.[6][7][4] Even though both enzyme families attach sugars to nitrogen, the Haemophilus influenzae N-glycosyltransferase bears no similarity to the oligosaccharyltransferases[8] and appears to have evolved independently.[1]
  2. carrier,[24] with a variety of oligosaccharides used.[26]

References

  1. ^ a b c Nothaft & Szymanski 2013, p. 6916.
  2. ^ Choi et al. 2010, p. 2.
  3. ^ a b Song et al. 2017, p. 8856.
  4. ^ a b c Naegeli & Aebi 2015, p. 11.
  5. ^ Nothaft & Szymanski 2013, p. 6912.
  6. ^
    PMID 20523900
    .
  7. ^ a b c d Gawthorne et al. 2014, p. 633.
  8. ^ a b c d e f g h Naegeli et al. 2014, p. 24522.
  9. ^ a b Naegeli et al. 2014, p. 24521.
  10. ^ Piniello, Macías-León & Miyazaki 2023, p. 8.
  11. ^ Bause & Legler 1981, p. 644.
  12. ^ a b c d e f g Schwarz et al. 2011, p. 35273.
  13. ^ a b c d e f g Schwarz et al. 2011, p. 35267.
  14. ^ a b Piniello, Macías-León & Miyazaki 2023, p. 2.
  15. ^ Song et al. 2017, p. 8861.
  16. PMID 6847620
    .
  17. ^ a b Naegeli et al. 2014, p. 24524.
  18. ^ Naegeli et al. 2014, p. 24530.
  19. ^ Choi et al. 2010, p. 7.
  20. ^ a b Naegeli et al. 2014, p. 2171.
  21. ^ Kawai et al. 2011, p. 38553.
  22. ^ a b McCann & St Geme 2014, p. 2.
  23. ^ a b Choi et al. 2010, p. 1.
  24. ^ a b c d Naegeli et al. 2014, p. 2170.
  25. ^ Bause & Legler 1981, p. 639.
  26. ^ a b Naegeli & Aebi 2015, p. 4.
  27. ^ Grass et al. 2003, p. 737.
  28. ^ Schwarz et al. 2011, p. 35269.
  29. ^ Gawthorne et al. 2014, p. 636.
  30. ^ a b Song et al. 2017, p. 8857.
  31. ^ a b c McCann & St Geme 2014, p. 3.
  32. ^ Naegeli & Aebi 2015, p. 12.
  33. ^ Naegeli et al. 2014, p. 2172.
  34. PMID 29101090
    .
  35. ^ Naegeli et al. 2014, p. 2173.
  36. ^ a b Naegeli et al. 2014, p. 2178.
  37. ^ a b Naegeli et al. 2014, p. 24531.
  38. ^ Gawthorne et al. 2014, p. 634.
  39. ^ Kawai et al. 2011, p. 38547.
  40. ^ Kawai et al. 2011, p. 38549,38550.
  41. ^ Cuccui et al. 2017, p. 2.
  42. ^ Cuccui et al. 2017, p. 10.
  43. ^ a b c Rempe et al. 2015, p. 5.
  44. ^ a b Rempe et al. 2015, p. 4.
  45. ^ a b c McCann & St Geme 2014, p. 1.
  46. ^ Rempe et al. 2015, p. 2.
  47. ^ Gawthorne et al. 2014, p. 637,638.
  48. ^ Grass et al. 2003, p. 742.
  49. ^ Kawai et al. 2011, p. 38546.
  50. ^
    PMID 27107636
    .
  51. ^ Rempe et al. 2015, p. 3.
  52. ^ Rempe et al. 2015, p. 6.

Sources

External links

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