Chemical models of peptide formation in translation.
Chemical models of peptide formation in translation.
复制标题
翻译过程中肽形成的化学模型。
DOI：
10.1021/bi1000273
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发表时间：
2010
期刊：
影响因子：
2.9
通讯作者：
Forster,AnthonyC
中科院分区：
文献类型：
--
作者：
Watts,REdward;Forster,AnthonyC
包括脯氨酸在内的N-烷基氨基酸的核糖体掺入比非N-烷基氨基酸的掺入慢。化学反应性假说提出，这些结果以及从遗传密码中排除非脯氨酸N-烷基氨基酸可以通过氨基酸亲核体的固有化学反应性来解释。然而，与生理条件相关的反应性的数据很少。在这里，我们使用甲酰甲硫氨酸-N-羟基琥珀酰亚胺酯的非酶促水基缓冲反应来模拟二肽形成中的 11 种氨基酸亲核试剂。非酶系统和翻译系统中的相对速率相关性良好，支持化学反应性假说，并认为肽键形成而不是调节是天然 Pro-tRNAProiso受体的速率限制。在化学模型中评估了 N-取代位阻、侧链位阻、诱导和 pKa 的影响。发现影响相对速率的主要因素是N-取代位阻。
Ribosomal incorporations ofN-alkyl amino acids including proline are slower than incorporations of non-N-alkyll-amino acids. The chemical reactivity hypothesis proposes that these results and the exclusion of nonprolineN-alkyl amino acids from the genetic code are explained by intrinsic chemical reactivities of the amino acid nucleophiles. However, there is little data on the reactivities relevant to physiological conditions. Here, we use nonenzymatic, aqueous-based, buffered reactions with formylmethionine-N-hydroxysuccinimide ester to model 11 amino acid nucleophiles in dipeptide formation. The relative rates in the nonenzymatic and translation systems correlate well, supporting the chemical reactivity hypothesis and arguing that peptide bond formation, not accommodation, is rate limiting for natural Pro-tRNAProisoacceptors. The effects ofN-substitution sterics, side chain sterics, induction, and pKawere evaluated in the chemical model. The dominant factor affecting relative rates was found to beN-substitution sterics.