Here’s a concise Pharm-D level summary of major post-translational modifications (PTMs),
their significance, and examples:
1. Phosphorylation
Description: Addition of a phosphate group (PO₄³⁻) to Ser, Thr, or Tyr
residues.
Significance: Regulates enzyme activity, signal transduction, cell
cycle.
Example: Activation of glycogen phosphorylase by phosphorylation;
targeted in cancer therapies (e.g., tyrosine kinase inhibitors like
imatinib).
2. Acetylation
Description: Addition of an acetyl group (COCH₃) to lysine residues.
Significance: Affects gene expression by modifying histones; protein
stability.
Example: Histone acetylation promotes gene transcription; targeted
by HDAC inhibitors (e.g., vorinostat in cancer).
3. Methylation
Description: Addition of one or more methyl groups (CH₃) to arginine
or lysine.
Significance: Regulates gene expression, chromatin structure, protein
function.
Example: DNA methylation in epigenetics; methylation of histones
controls transcription.
4. Ubiquitination
Description: Attachment of ubiquitin protein to lysine residues.
Significance: Marks proteins for degradation via the proteasome.
Example: p53 regulation; proteasome inhibitors like bortezomib used
in multiple myeloma.
5. Sumoylation
Description: Addition of SUMO (Small Ubiquitin-like Modifier) proteins.
Significance: Alters nuclear transport, transcription, and DNA repair.
Example: Regulates p53 activity; defects associated with
neurodegenerative diseases.
6. Lipidation
Description: Attachment of lipid molecules (e.g., myristoyl, prenyl,
palmitoyl).
Significance: Anchors proteins to membranes; essential for signal
transduction.
Example: Ras protein requires farnesylation for membrane localization
(targeted in cancer).
7. Glycosylation
Description: Addition of carbohydrate chains to Asn (N-linked) or
Ser/Thr (O-linked).
Significance: Enhances protein folding, stability, and immune
recognition.
Example: Glycosylated antibodies in monoclonal therapies (e.g.,
rituximab); EPO used in anemia.
8. Nitrosylation
Description: Addition of a nitric oxide (NO) group to cysteine residues.
Significance: Regulates protein function and cell signaling.
Example: S-nitrosylation of caspases in apoptosis; implicated in
neurodegenerative diseases.
9. Hydroxylation
Description:
Addition of a hydroxyl group (-OH) to amino acid side chains, commonly proline or lysine.
Enzyme:
Hydroxylases (e.g., prolyl hydroxylase), require vitamin C (ascorbic acid) as a cofactor.
Significance:
Stabilizes collagen triple-helix structure.
Involved in oxygen sensing via hypoxia-inducible factor (HIF) regulation.
Example:
Collagen synthesis: Hydroxylation of proline and lysine residues is essential. Deficiency causes
scurvy (vitamin C deficiency).
HIF-1α hydroxylation targets it for degradation under normal oxygen conditions.