Regiospecificity of the peptidyl tRNA ester within the ribosomal P site.
The ribosomal peptidyl transferase center is expected to be regiospecific with regard to its tRNA substrates, yet the ester linkages between the tRNA and the amino acid or peptide are susceptible to isomerization between the O2' and O3' hydroxyls of the terminal A76 ribose sugar. To establish which isomer of the P site tRNA ester is utilized by the ribosome, we prepared two nonisomerizable transition state inhibitors with either an A76 O2' or O3' linkage. Strong preferential binding to the O3' regioisomer indicates that the peptidyl transferase proceeds through a transition state with an O3'-linked peptide in the P-site.
Huang
Kevin S
KS
Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, Connecticut 06520-8114, USA.
Weinger
Joshua S
JS
Butler
Ethan B
EB
Strobel
Scott A
SA
D001665:Binding Sites; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012343:RNA, Transfer / Q000378:metabolism*; D012270:Ribosomes / Q000201:enzymology / Q000378:metabolism*; D013033:Sparsomycin / Q000378:metabolism; D013379:Substrate Specificity
D013033:Sparsomycin; D012343:RNA, Transfer; D010458:Peptidyl Transferases