8GIJ

TEM-1 Beta Lactamase Variant 80.b

8GIJ の概要

• エントリーDOI: 10.2210/pdb8gij/pdb
• 関連するPDBエントリー: 8GII 8OF9
• 分子名称: TEM-1 Beta Lactmase Variant 80.b (2 entities in total)
• 機能のキーワード: tem-1, tem1, beta-lactamase, class a beta lactamase, hydrolase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 56786.53

構造登録者

Fram, B.F.,Gauthier, N.P.,Khan, A.,Sander, C. (登録日: 2023-03-14, 公開日: 2024-04-17, 最終更新日: 2024-07-17)

主引用文献

Fram, B.,Su, Y.,Truebridge, I.,Riesselman, A.J.,Ingraham, J.B.,Passera, A.,Napier, E.,Thadani, N.N.,Lim, S.,Roberts, K.,Kaur, G.,Stiffler, M.A.,Marks, D.S.,Bahl, C.D.,Khan, A.R.,Sander, C.,Gauthier, N.P.
Simultaneous enhancement of multiple functional properties using evolution-informed protein design.
Nat Commun, 15:5141-5141, 2024

PubMed Abstract: A major challenge in protein design is to augment existing functional proteins with multiple property enhancements. Altering several properties likely necessitates numerous primary sequence changes, and novel methods are needed to accurately predict combinations of mutations that maintain or enhance function. Models of sequence co-variation (e.g., EVcouplings), which leverage extensive information about various protein properties and activities from homologous protein sequences, have proven effective for many applications including structure determination and mutation effect prediction. We apply EVcouplings to computationally design variants of the model protein TEM-1 β-lactamase. Nearly all the 14 experimentally characterized designs were functional, including one with 84 mutations from the nearest natural homolog. The designs also had large increases in thermostability, increased activity on multiple substrates, and nearly identical structure to the wild type enzyme. This study highlights the efficacy of evolutionary models in guiding large sequence alterations to generate functional diversity for protein design applications.

PubMed: 38902262
DOI: 10.1038/s41467-024-49119-x

実験手法

X-RAY DIFFRACTION (1.59 Å)