Table 1.
Consensus motifs and enzymes responsible for therapeutic modifications.
| Modification type | Linkage | Consensus sequence | Enzymes |
|---|---|---|---|
| N-glycosylation | GlcNAc-Asn | N-X-(S/T), X≠Pro | OST |
| Mucin-type O-glycosylation |
GalNAc-Ser/Thr | No consensus, Pro favorable | ppGalNAcT |
| Disulfide bond | –S–S– | Cysteine pairs | Ero1-PDI |
| γ-carboxylation | Glu→Gla | Mediated by adjacent propeptide | GGCX-VKOR |
| β-hydroxylation | Asn→Hyn; Asp→Hya | C-X-D/N-X-X-X-X-F/Y-X-C-X-C but not sufficient |
β-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 |