Peptidyl transferase center explained

Peptidyl transferase
Ec Number:	2.3.2.12
Cas Number:	9059-29-4

The peptidyl transferase center is an aminoacyltransferase ribozyme (RNA enzyme) located in the large subunit of the ribosome. It forms peptide bonds between adjacent amino acids during the translation process of protein biosynthesis.^[1] It is also responsible for peptidyl-tRNA hydrolysis, allowing the release of the synthesized peptide chain at the end of translation.^[2] Peptidyl transferase activity is not mediated by any ribosomal proteins, but entirely by ribosomal RNA (rRNA). The peptidyl transferase center is a significant piece of evidence supporting the RNA World hypothesis.

In prokaryotes, the 50S (23S component) ribosomal subunit contains the peptidyl transferase center and acts as a ribozyme. The peptidyl transferase center on the 50S subunit lies at the lower tips (acceptor ends) of the A- and P- site tRNAs.^[3]

In eukaryotes, the 60S (28S component) ribosomal subunit contains the peptidyl transferase center and acts as the ribozyme.

Peptidyl transferases are not limited to translation, but there are relatively few enzymes with this function.

Mechanism

The substrates for the peptidyl transferase reaction are two tRNA molecules: one in the peptidyl site, bearing the growing peptide chain, and the other in the aminoacyl site, bearing the amino acid that will be added to the chain. The peptidyl chain and the incoming amino acid are attached to their respective tRNAs via ester bonds to the oxygen atom at the 3' ends of these tRNAs. The 3' ends of all tRNAs share a universally conserved CCA sequence.^[4] The alignment between the CCA ends of the ribosome-bound peptidyl tRNA and aminoacyl tRNA in the peptidyl transferase center contribute to peptide bond formation by providing the proper orientation for the reaction to occur.^[5] This reaction occurs via nucleophilic displacement. The amino group of the aminoacyl tRNA attacks the terminal carbonyl group of the peptidyl tRNA. The reaction proceeds through a tetrahedral intermediate and the loss of the P site tRNA as a leaving group.

In peptidyl-tRNA hydrolysis, the same mechanism is used, but with a water molecule as the nucleophile.

Antibiotic inhibitors

The following protein synthesis inhibitors target the peptidyl transferase center:

• Chloramphenicol binds^[6] to residues A2451 and A2452 in the 23S rRNA of the ribosome and inhibits peptide bond formation.
• Pleuromutilins also bind to the peptidyl transferase center.^[7]
• Macrolide antibiotics are thought to inhibit peptidyl transferase, in addition to inhibiting ribosomal translocation.^[8]

See also

• Enzyme
• Ribozyme
• Transferase
• Translation

Notes and References

1. Tirumalai MR, Rivas M, Tran Q, Fox GE . The Peptidyl Transferase Center: a Window to the Past . Microbiology and Molecular Biology Reviews . 85 . 4 . e0010421 . December 2021 . 34756086 . 8579967 . 10.1128/MMBR.00104-21 .
2. Polacek N, Mankin AS . The ribosomal peptidyl transferase center: structure, function, evolution, inhibition . Critical Reviews in Biochemistry and Molecular Biology . 40 . 5 . 285–311 . January 2005 . 16257828 . 10.1080/10409230500326334 .
3. Book: Garrett RH, Grisham CM . Biochemistry . Brooks/Cole . 2012 . 978-1-133-10629-6 . 5th . Belmont CA .
4. Hou YM . CCA addition to tRNA: implications for tRNA quality control . IUBMB Life . 62 . 4 . 251–260 . April 2010 . 20101632 . 2848691 . 10.1002/iub.301 .
5. Moore PB, Steitz TA . After the ribosome structures: how does peptidyl transferase work? . RNA . 9 . 2 . 155–159 . February 2003 . 12554855 . 1370378 . 10.1261/rna.2127103 .
6. Gu Z, Harrod R, Rogers EJ, Lovett PS . Anti-peptidyl transferase leader peptides of attenuation-regulated chloramphenicol-resistance genes . Proceedings of the National Academy of Sciences of the United States of America . 91 . 12 . 5612–5616 . June 1994 . 7515506 . 44046 . 10.1073/pnas.91.12.5612 . free . 1994PNAS...91.5612G .
7. Long KS, Hansen LH, Jakobsen L, Vester B . Interaction of pleuromutilin derivatives with the ribosomal peptidyl transferase center . Antimicrobial Agents and Chemotherapy . 50 . 4 . 1458–1462 . April 2006 . 16569865 . 1426994 . 10.1128/AAC.50.4.1458-1462.2006 .
8. Web site: Protein synthesis inhibitors: macrolides mechanism of action animation. Classification of agents . https://web.archive.org/web/20081226204524/http://pharmamotion.com.ar/protein-synthesis-inhibitors-macrolides-mechanism-of-action-animation-classification-of-agents/ . dead . December 26, 2008 . Pharmamotion . Kaiser G . The Community College of Baltimore County . July 31, 2009 .