| Peptidyl transferase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 2.3.2.12 | ||||||||
| CAS no. | 9059-29-4 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| |||||||||
The peptidyl transferase center (EC 2.3.2.12, PTC) 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 catalytic activity of the PTC is a significant piece of evidence supporting the RNA World hypothesis. [2] The PTC is a highly conserved region with a very slow rate of mutation. It is considered to be among the most ancient elements of the ribosome, probably predating the last universal common ancestor. [3]
The position of the PTC is analogous in all ribosomes (domain V in 23S numbering), being a part of the large subunit ribosomal RNA with the name only varying due to the different size in Svedberg. It acts as a ribozyme at the lower tips (acceptor ends) of the A- and P- site tRNAs. The different names include: [4] : 1062
Peptidyl transferases are not limited to translation, but there are relatively few enzymes with this function.[ citation needed ]
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. [4] : 437–8 The 3' ends of all tRNAs share a universally conserved CCA sequence. [5] 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. [6] 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]
Timing: Bokov and Steinberg (2009) "unwrapped" the 23S rRNA structure into several layers of contact. In their model, the PTC is the original element of 23S rRNA, to which structual features were later added. [7] An opposing view from Caetano-Anollés and Sun (2014) is that the tRNA's acceptor arm and the aaRS's catalytic domain came earlier than the genetic code and the PTC. [8]
Ancestor:
A designed minimized version of E. coli PTC from 2024 was able to fold into a PTC-like shape without the help of ribosomal proteins and bind tRNA analogues at the P-site and the A-site. It fails to form peptide bonds due to binding the molecules in the wrong orientation. [3]
The following protein synthesis inhibitors target the peptidyl transferase center:
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