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BL4010 PROTEIN MODIFICATION 1. Proteolytic processing 2. Phosphorylation 3. Sulfonation 4. Amidation 5. Glycosylation 6. Hydroxylation 7. Ubiquitination 8. Addition of prosthetic groups 9. Iodination 10. Adenylation 11. Prenylation a. Farnesylation b. Geranylgeranylation 12. Myristoylation 13. Alkylation a. Methylation b. Acetylation 14. Crosslinking 15. N-Glutamyl cyclization 16. Carboxylation 17. Cyclization 18. GPI anchor N-terminal modification Proteolytic processing Signal peptide (pre-peptide) Endopeptidase (pro-peptide) Aminopeptidase Acetylation Glutamyl cyclization Myristoylation (on Cys) Deformylase (formyl Met) Methylation of Ala Acetylation of Ser page 1 ALA CYS: 8, 10, 12, 13a, 14, ASP: 2, 4,13a, 16 GLU: 4, 13a, 16, 17 PHE: GLY: 6 HIS: 2, 8, 13a ILE LYS: 1, 6, 7, 8, 10, 13a, 13,b, 14, 16 LEU MET: 8 ASN: 5, 16, 13a, HYP: 5, 13a PRO: 6, GLN: 13a, ARG: 1, 13a, SER: 2, 3, 5, 8, 13 THR: 2, 3, 5, 8, 13 VAL TRP: 6 TYR: 8, 9, 10, 14, 2 N-term: 1, 13b, 17 C-term: 4, 13a, 11, 18 C-terminal modifications Proteolytic processing Endopeptidase Carboxypeptidase Amidation Prenylation Farnesylation Geranylgeranylation GPI anchor BL4010 PROTEIN MODIFICATION GROUP SPECIFIC MODIFICATION (not every amino acid bearing these groups will get modified!!) Hydroxyl modification Phosphorylation ( ~OH ~OPO4-) Sulfonation (~OH ~OSO3Methylation (~OH ~OCH3) Glycosylation (~OH ~OGalNac-) Prosthetic groups (metal binding) Amino modification Methylation (~NH2 ~NHCH3) Acetylation (~NH2 NHCOCH3) Carboxylation (~NH2 ~NHCOO-) Myristoylation (~NH2 ~NHCO) Glycosylation (~NH2 ~OGlcNac) Adenylation (~NH2 ~NHOADP) Hydroxylation (~NH2 ~NHOH) Imino modification Methylation (>NH >NCH3) Phosphorylation (>NH >NOPO3-) Prosthetic groups (metals, heme) Carboxyl modification Amidation (COO- COONH2) GPI anchor (COO- COglycerylPI) Prosthetic groups (metal binding) Sulhydryl modification Acylation (SH S) Cross-linking (SH S-S) Methylation (SH SCH3) Prosthetic groups (metal binding) Prenylation (SH S) Indole modification Hydroxylation (>NH >NOH) page 2