2. Introduction
• It is the chemical modification of protein after its
translation.
• Key role in functional Proteomics.
• They regulate activity, localization and interaction
with other cellular molecules such as proteins, nucleic
acids, lipids and cofactors.
3. Types of Post Translational
Modifications of Proteins
Phosphorylation
Glycosylation
Ubiquitination
S-Nitrosylation
Methylation
N-Acetylation
Lipidation
Proteolysis
4. Phosphorylation
• Addition of phosphate group to a protein.
• Principally on serine, threonine or tyrosine
residues.
• Also known as Phosphoregulation.
• Critical role in cell cycle, growth, apoptosis and signal
transduction pathways.
Protein kinases
ATP + protein ———————> phosphoprotein + ADP
5. Glycosylation
• The covalent attachment of oligosaccharides
• Addition of glycosyl group or carbohydrate group to a
protein.
• Principally on Asparagine, hydroxylysine, serine or
threonine.
• Significant effect on protein folding, conformation,
distribution, stability and activity.
6. Classes of Glycans
• N-Linked glycans – attached to nitrogen of Asparagine or
arginine side
chains.
• O-Linked glycans – attached to hydroxy oxygen of
serine,threonine
• Phosphoglycans – linked through the phosphate of serine.
• C-Linked glycans – Rare form, Sugar is added to a carbon
on tryptophan side chain.
7. Ubiquitination
• Ubiquitin is a small regulatory protein that can
be attached to the proteins and label them for
destruction.
• Effects in cell cycle regulation, control of proliferation
and differentiation, programmed cell death (apoptosis),
DNA repair, immune and inflammatory processes and
organelle biogenesis.
8. S-Nitrosylation
• Nitrosyl (NO) group is added to the protein.
• NO a chemical messanger that reacts with free
cysteine residues to form S-nitrothiols.
• Used by cells to stabilize proteins, regulate
gene expression.
9. Alkylation/Methylation
• Addition of methyl group to a protein.
• Usually at lysine or arginine residues.
• Binds on nitrogen and oxygen of proteins
• Enzyme for this is methyltransferase
• Methylation of lysine residues in histones in DNA is
important regulator of chromatin structure.
10. N-Acetylation
• Addition of acetyl group to the nitrogen.
• Histones are acetylated on lysine residues in the N-
terminal tail as a part of gene regulation.
• Involved in regulation of transcription factors,
effector proteins, molecular chaperons and cytoskeletal
proteins.
• Methionine aminopeptidase (MAP) is an enzyme
responsible for N-terminal acetylation
11. Lipidation
• Lipidation attachment of a lipid group, such as
a fatty acid, covalently to a protein.
• In general, lipidation helps in cellular localization and
targeting signals, membrane tethering and as mediator
of protein-protein interactions.
