An Induced-fit Mechanism to Promote Peptidyl Bond Formation and Exclude Hydrolysis of Peptidyl-tRNA
The large ribosomal subunit catalyses the reaction between the {alpha}-amino group of the aminoacyl-tRNA bound to the A site and the ester carbon of the peptidyl-tRNA bound to the P site1, while preventing the nucleophilic attack of water on the ester, which would lead to unprogrammed deacylation of the peptidyl-tRNA. Here we describe three new structures of the large ribosomal subunit of Haloarcula marismortui (Hma) complexed with peptidyl transferase substrate analogues that reveal an induced-fit mechanism in which substrates and active-site residues reposition to allow the peptidyl transferase reaction. Proper binding of an aminoacyl-tRNA analogue to the A site induces specific movements of 23S rRNA nucleotides 2618-2620 (Escherichia coli numbering 2583-2585) and 2541(2506), thereby reorienting the ester group of the peptidyl-tRNA and making it accessible for attack. In the absence of the appropriate A-site substrate, the peptidyl transferase center positions the ester link of the peptidyl-tRNA in a conformation that precludes the catalyzed nucleophilic attack by water. Protein release factors2 may also function, in part, by inducing an active-site rearrangement similar to that produced by the A-site aminoacyl-tRNA, allowing the carbonyl group and water to be positioned for hydrolysis.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 913874
- Report Number(s):
- BNL-78442-2007-JA; NATUAS; TRN: US200804%%259
- Journal Information:
- Nature, Vol. 438; ISSN 0028-0836
- Country of Publication:
- United States
- Language:
- English
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