This presentation is targeted for MBBS, MD, BDS students depicting the process of protein synthesis and its biomedical significance

1. POST-TRANSLATIONAL MODIFICATION
Prof (Dr) V P AcharyaMD,PhD
KIMS & PBH Hospital, Bhubaneswar

2. Post-translational modification of Polypeptide
Protein folding
Proteolytic cleavage Intein splicing
Covalent modification
Different structures
Insulin, Zymogens
Inteins removed & Exteins spliced
a. Phosphorylation
b. Hydroxylation
c. Glycosylation
d. Carboxylation
e. Ubiquitylation

3. Amino terminal and carboxyl terminal
modifications
 1st residue- N- formylmethionine (bacteria) or
Met (eukaryotes)
 Formyl group and amino terminal residues is
mostly removed
 50% eukaryotic proteins- NH3 group of amino
terminal residue is N-acetylated
 Carboxyl terminal also may be modified
 15-30 residues at the amino-terminal act as
signal sequences to direct a protein to its
target– later they are removed

4. Modifications of individualAA residues
 Phosphorylation- -OH groups of Ser,Thr ,Tyr are
enzymatically phosphorylated by ATP– adds
negative charge to the protein
 Casein binds to Ca+2 due to this negative charge due
to phosphoserine groups
 Phosphorylation and dephosphorylation regulate
many enzymes and proteins
 Carboxylation - γ- carboxylation of Prothrombin-
requiresVitamin K
 Glycosylation - N-linked oligosaccharides (attached
to Asn) and O- linked oligosaccharides (Ser/Thr
residues)
 Isoprenylation - thioether bond formed between Cys
and isoprene

5. Additionof prosthetic groups
 Prosthetic groups bound to proteins by
covalent groups
 Hb / Cyt C- Heme group
 Biotin- Acetyl CoA-carboxylase

6.  Proteolytic processing- Proinsulin, viral
proteins, proteases
 Formation of disulfide cross-links- Insulin

7. Inhibitors ofTranslation
A. Reversible inhibitor
a.Tetracyclin– Binds to 30s ribosome
↓
Inhibit attachment of aminoacyl tRNA to the A site
(bacteriostatic)
b. Chloramphenicol– Inhibits peptidyl
transferase- prevents elongation of peptide
chain
c. Erythromycin & Clindamycin– Prevent
translocation by binding to 50s subunit of
bacterial ribosome

8. B.Irreversibleinhibitor
Streptomycin and
Aminoglycosides—Bind to 30s ribosomal sub-
unit
Low conc.- Misreading of protein
↓
Useless bacterial proteins
Pharma. Conc.- Inhibit IC synthesis
↓
Protein synthesis inhibited

9. C. Inhibitors in mammals
1. Puromycin– Structural analogue of tyrosinyl t-
RNA
2. Cycloheximide– Inhibits peptidyl transferase
3. Diphtheria toxin—Inactivation of EF-2 by
attachment of ADP to EF-2
4. Ricin– Inactivates 28s rRNA

10. KNOWLEDGE HAS NO COPYRIGHT

11. ProteinTargeting/Sortingofproteins

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