8U5A

Improving protein expression, stability, and function with ProteinMPNN

8U5A の概要

• エントリーDOI: 10.2210/pdb8u5a/pdb
• 分子名称: Designed myoglobin, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total)
• 機能のキーワード: protein expression, stability, function, proteinmpnn, de novo design, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40210.98

構造登録者

Kalvet, I.,Bera, A.K.,Baker, D. (登録日: 2023-09-12, 公開日: 2024-01-17, 最終更新日: 2024-01-31)

主引用文献

Sumida, K.H.,Nunez-Franco, R.,Kalvet, I.,Pellock, S.J.,Wicky, B.I.M.,Milles, L.F.,Dauparas, J.,Wang, J.,Kipnis, Y.,Jameson, N.,Kang, A.,De La Cruz, J.,Sankaran, B.,Bera, A.K.,Jimenez-Oses, G.,Baker, D.
Improving Protein Expression, Stability, and Function with ProteinMPNN.
J.Am.Chem.Soc., 146:2054-2061, 2024

PubMed Abstract: Natural proteins are highly optimized for function but are often difficult to produce at a scale suitable for biotechnological applications due to poor expression in heterologous systems, limited solubility, and sensitivity to temperature. Thus, a general method that improves the physical properties of native proteins while maintaining function could have wide utility for protein-based technologies. Here, we show that the deep neural network ProteinMPNN, together with evolutionary and structural information, provides a route to increasing protein expression, stability, and function. For both myoglobin and tobacco etch virus (TEV) protease, we generated designs with improved expression, elevated melting temperatures, and improved function. For TEV protease, we identified multiple designs with improved catalytic activity as compared to the parent sequence and previously reported TEV variants. Our approach should be broadly useful for improving the expression, stability, and function of biotechnologically important proteins.

PubMed: 38194293
DOI: 10.1021/jacs.3c10941

実験手法

X-RAY DIFFRACTION (2 Å)