Physocarpus

by | Mar 16, 2018 | Physocarpus

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The peptidyl transferase center (EC 2.3.2.12) 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.[2]

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]: 1062 

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.[citation needed]

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.[3]: 437–8  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.[2]

In peptidyl-tRNA hydrolysis, the same mechanism is used, but with a water molecule as the nucleophile.[2]

Antibiotic inhibitors

The following protein synthesis inhibitors target the peptidyl transferase center:

See also

References

  1. ^ Tirumalai MR, Rivas M, Tran Q, Fox GE (December 2021). "The Peptidyl Transferase Center: a Window to the Past". Microbiology and Molecular Biology Reviews. 85 (4): e0010421. doi:10.1128/MMBR.00104-21. PMC 8579967. PMID 34756086.
  2. ^ a b c d Polacek N, Mankin AS (January 2005). "The ribosomal peptidyl transferase center: structure, function, evolution, inhibition". Critical Reviews in Biochemistry and Molecular Biology. 40 (5): 285–311. doi:10.1080/10409230500326334. PMID 16257828.
  3. ^ a b Garrett RH, Grisham CM (2012). Biochemistry (5th ed.). Belmont CA: Brooks/Cole. ISBN 978-1-133-10629-6.
  4. ^ Hou YM (April 2010). "CCA addition to tRNA: implications for tRNA quality control". IUBMB Life. 62 (4): 251–260. doi:10.1002/iub.301. PMC 2848691. PMID 20101632.
  5. ^ Moore PB, Steitz TA (February 2003). "After the ribosome structures: how does peptidyl transferase work?". RNA. 9 (2): 155–159. doi:10.1261/rna.2127103. PMC 1370378. PMID 12554855.
  6. ^ Gu Z, Harrod R, Rogers EJ, Lovett PS (June 1994). "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. Bibcode:1994PNAS...91.5612G. doi:10.1073/pnas.91.12.5612. PMC 44046. PMID 7515506.
  7. ^ Long KS, Hansen LH, Jakobsen L, Vester B (April 2006). "Interaction of pleuromutilin derivatives with the ribosomal peptidyl transferase center". Antimicrobial Agents and Chemotherapy. 50 (4): 1458–1462. doi:10.1128/AAC.50.4.1458-1462.2006. PMC 1426994. PMID 16569865.
  8. ^ Kaiser G. "Protein synthesis inhibitors: macrolides mechanism of action animation. Classification of agents". Pharmamotion. The Community College of Baltimore County. Archived from the original on December 26, 2008. Retrieved July 31, 2009.
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