Structural insights into peptide bond formation

被引:222
作者
Hansen, JL
Schmeing, TM
Moore, PB
Steitz, TA
机构
[1] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA
[2] Yale Univ, Dept Chem, New Haven, CT 06520 USA
[3] Howard Hughes Med Inst, New Haven, CT 06520 USA
关键词
D O I
10.1073/pnas.172404099
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The large ribosomal subunit catalyzes peptide bond formation and will do so by using small aminoacyl- and peptidyl-RNA fragments of tRNA. We have refined at 3-Angstrom resolution the structures of both A and P site substrate and product analogues, as well as an intermediate analogue, bound to the Haloarcula marismortui 50S ribosomal subunit. A P site substrate, CCA-Phe-caproic acid-biotin, binds equally to both sites, but in the presence of sparsomycin binds only to the P site. The CCA portions of these analogues are bound identically by either the A or P loop of the 23S rRNA. Combining the separate P and A site substrate complexes into one model reveals interactions that may occur when both are present simultaneously. The alpha-NH2 group of an aminoacylated fragment in the A site forms one hydrogen bond with the N3 of A2486 (2451) and may form a second hydrogen bond either with the 2' CH of the A-76 ribose in the P site or with the 2' OH of A2486 (2451). These interactions position the alpha amino group adjacent to the carbonyl carbon of esterified P site substrate in an orientation suitable for a nucleophilic attack.
引用
收藏
页码:11670 / 11675
页数:6
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