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Production of Pharmaceuticals
Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under sterile, tightly...
Protein Modifications in the RER
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
tRNA Activation
Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...
Translocation of Proteins into the Mitochondria
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
Protein Folding
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
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ソルターゼによって活性化されたタンパク質チオエステル合成.
Jingjing J Ling1, Rocco L Policarpo, Amy E Rabideau
1Department of Chemistry, Massachusetts Institute of Technology, 16-573a, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Journal of the American Chemical Society
|June 13, 2012
まとめ
研究者たちは,タンパク質半合成に不可欠なタンパク質チオエステルを生成するためにソルターゼAを用いた新しいシンプルな方法を開発しました. この技術は,高度なタンパク質工学と結合戦略を容易にする.
科学分野:
- バイオケミストリー バイオケミストリー
- プロテイン工学は,タンパク質の
- 合成生物学 合成生物学とは
背景:
- C端のチオエステルを持つタンパク質は,タンパク質半合成における重要な中間物質である.
- タンパク質チオエステル合成の現在の方法は,主に人工知能に依存しています.
研究 の 目的:
- C端末 (α) ティオエステルによる再結合タンパク質の製造のための単純で日常的な戦略を導入する.
- 複雑なタンパク質構造の合成におけるこの方法の有用性を実証する.
主な方法:
- C端末 (α) ティオエステルを含む再結合タンパク質の製造のために使用されたソルターゼA.
- この方法を適用して,炭毒素の2種類の貨物タンパク質を合成し,1つは (α) チオエステル,もう1つはD-ポリペプチドセグメントを含んでいる.
- 保護性抗原孔を通してこれらの変異体の転位を評価した.
主要な成果:
- ソーターゼAを用いてC端末 (α) ティオエステルによる再結合タンパク質を成功裏に製造した.
- ドメイン間のD-ポリペプチドセグメントを含むタンパク質の合成を実証した.
- 両方のエンジニアリングされたタンパク質の変種が,保護性抗原孔を通って転位できることを確認しました.
結論:
- ソーターゼAベースの戦略は,タンパク質チオエステルを合成するためのシンプルで効率的な代替案を提供します.
- この方法により,ソルターゼ媒介結合と先端の化学結合を統合して,高度なタンパク質構築が可能になります.
- 開発された技術は,タンパク質半合成と複雑なバイオ分子工学の可能性を拡大します.

