論文 - 詳細
| RRC ID | 35638 |
|---|---|
| 著者 | Fung AW, Ebhardt HA, Krishnakumar KS, Moore J, Xu Z, Strazewski P, Fahlman RP. |
| タイトル | Probing the leucyl/phenylalanyl tRNA protein transferase active site with tRNA substrate analogues. |
| ジャーナル | Protein Pept Lett |
| Abstract |
Aminoacyl-tRNA protein transferases post-translationally conjugate an amino acid from an aminoacyl-tRNA onto the N-terminus of a target polypeptide. The eubacterial aminoacyl-tRNA protein transferase, L/F transferase, utilizes both leucyl-tRNA(Leu) and phenylalanyl-tRNA(Phe) as substrates. X-ray crystal structures with substrate analogues, the minimal substrate phenylalanyl adenosine (rA-Phe) and inhibitor puromycin, have been used to characterize tRNA recognition by L/F transferase. However analyses of these two X-ray crystal structures reveal significant differences in binding. Through structural analyses, mutagenesis, and enzymatic activity assays, we rationalize and demonstrate that the substrate analogues bind to L/F transferase with similar binding affinities using a series of different interactions by the various chemical groups of the analogues. Our data also demonstrates that enlarging the hydrophobic pocket of L/F transferase selectively enhances puromycin inhibition and may aid in the development of improved inhibitors for this class of enzymes. |
| 巻・号 | 21(7) |
| ページ | 603-14 |
| 公開日 | 2014-7-1 |
| DOI | 10.2174/0929866521666140212110639 |
| PII | PPL-EPUB-59140 |
| PMID | 24521222 |
| MeSH | Aminoacyltransferases* / antagonists & inhibitors Aminoacyltransferases* / chemistry Aminoacyltransferases* / metabolism Catalytic Domain Crystallography, X-Ray Escherichia coli Proteins Mass Spectrometry Models, Molecular Mutation Protein Binding Puromycin / pharmacology RNA, Transfer, Leu / chemistry* RNA, Transfer, Leu / metabolism* RNA, Transfer, Phe / chemistry* RNA, Transfer, Phe / metabolism* Recombinant Fusion Proteins |
| IF | 1.156 |
| 引用数 | 3 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 原核生物(大腸菌) | NA |