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Post Translational Modifications

The document outlines major post-translational modifications (PTMs) including phosphorylation, acetylation, methylation, ubiquitination, sumoylation, lipidation, glycosylation, nitrosylation, and hydroxylation, detailing their descriptions, significance, and examples. Each PTM plays a crucial role in regulating various biological processes such as enzyme activity, gene expression, protein stability, and cellular signaling. Specific examples highlight their relevance in therapeutic contexts, particularly in cancer and genetic disorders.

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0% found this document useful (0 votes)
63 views3 pages

Post Translational Modifications

The document outlines major post-translational modifications (PTMs) including phosphorylation, acetylation, methylation, ubiquitination, sumoylation, lipidation, glycosylation, nitrosylation, and hydroxylation, detailing their descriptions, significance, and examples. Each PTM plays a crucial role in regulating various biological processes such as enzyme activity, gene expression, protein stability, and cellular signaling. Specific examples highlight their relevance in therapeutic contexts, particularly in cancer and genetic disorders.

Uploaded by

Areeba Fatima
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© © All Rights Reserved
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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.

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