Structural insights into peptide bond formation
Structural insights into peptide bond formation
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DOI：
10.1073/pnas.172404099
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发表时间：
2002-09-03
影响因子：
11.1
通讯作者：
Steitz, TA
中科院分区：
文献类型：
--
作者：
Hansen, JL;Schmeing, TM;Steitz, TA
大核糖体亚基催化肽键的形成，并将通过使用tRNA的小氨基酸和肽基rna片段来实现。我们在3埃分辨率下改进了A和P位点底物和产物类似物的结构，以及与Haloarcula marismortui 50S核糖体亚基结合的中间类似物。P位点底物cca - ph -己酸生物素与这两个位点结合相同，但在sparsomycin存在时仅与P位点结合。这些类似物的CCA部分与23S rRNA的A环或P环结合相同。将分离的P和A位点底物配合物结合到一个模型中，揭示了当两者同时存在时可能发生的相互作用。A位点氨基酰化片段的α - nh2基团与A2486（2451）的N3形成一个氢键，并可能与P位点A-76核糖的2′CH或A2486（2451）的2′OH形成第二个氢键。这些相互作用使与酯化P位底物的羰基碳相邻的α氨基处于适合亲核攻击的取向。
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.