Review Article
Biological Insights into Therapeutic Protein Modifications throughout Trafficking and Their Biopharmaceutical Applications
Table 1
Consensus motifs and enzymes responsible for therapeutic modifications.
| | Modification type | Linkage | Consensus sequence | Enzymes |
| | N-glycosylation | GlcNAc-Asn | N-X-(S/T), XPro | OST | Mucin-type
O-glycosylation | GalNAc-Ser/Thr | No consensus, Pro favorable | ppGalNAcT | | Disulfide bond | –S–S– | Cysteine pairs | Ero1-PDI | | -carboxylation | Glu→Gla | Mediated by adjacent propeptide | GGCX-VKOR | | -hydroxylation | Asn→Hyn; Asp→Hya | C-X-D/N-X-X-X-X-F/Y-X-C-X-C
but not sufficient | -hydroxylase | | Tyrosine sulfation | O4-sulfate ester | No simple consensus site
Glu/Asp around Tyr favorable | TPST1/TPST2 | | Propeptide cleavage | R/K | With single or pair of basic amino acids | PC family members | | Phosphorylation | pS, pT | S-x-E/pS or Ser/Thr | FAM20C or four-jointed | | Amidation | C-terminal carboxyl→amide | C-terminal glycine | PAM | | Deamidation | Asn→Asp; Gln→Glu | Asn-Gly most susceptible | Unknown or none | | Glycation | Ketoamine or Amadori product | N-terminal primary amine
Or amino group of lysine side chain | Unknown or none | | Pyroglutamate | Pyrrolidone carboxylic acid | N-terminal Gln or Glu | Unknown or none | | Oxidation | Met→Met sulfoxide | Met (Trp, Cys, Tyr, His) | Unknown or none | | Proteolytic processing | Arg ↓ or ↓ Lys | Basic amino acid | APC, carboxypeptidase B |
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