PMID:16306996
| Citation |
Schmeing, TM, Huang, KS, Strobel, SA and Steitz, TA (2005) An induced-fit mechanism to promote peptide bond formation and exclude hydrolysis of peptidyl-tRNA. Nature 438:520-4 |
|---|---|
| Abstract |
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 site, 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 centre positions the ester link of the peptidyl-tRNA in a conformation that precludes the catalysed nucleophilic attack by water. Protein release factors 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. |
| Links |
PubMed Online version:10.1038/nature04152 |
| Keywords |
Acylation; Archaeal Proteins/biosynthesis; Archaeal Proteins/chemistry; Archaeal Proteins/genetics; Archaeal Proteins/metabolism; Binding Sites; Haloarcula marismortui/chemistry; Haloarcula marismortui/genetics; Hydrolysis; Models, Molecular; Peptides/metabolism; Protein Biosynthesis; Protein Subunits/chemistry; Protein Subunits/metabolism; RNA, Ribosomal, 23S/genetics; RNA, Ribosomal, 23S/metabolism; RNA, Transfer/genetics; RNA, Transfer/metabolism; Ribosomes/chemistry; Ribosomes/genetics; Ribosomes/metabolism; Sparsomycin/metabolism; Water/chemistry; Water/metabolism |
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