8G1H

Ancestral protein AncTh of Phosphomethylpirimidine kinases family

8G1H の概要

• エントリーDOI: 10.2210/pdb8g1h/pdb
• 関連するPDBエントリー: 7R8Y 7R8Z
• 分子名称: Phosphomethylpyrimidine Kinase, 1,2-ETHANEDIOL, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: ancestral protein reconstruction, 5-phosphohydroxymethyl-2-methylpirimidine kinase, phosphomethylpirimidine kinases family, enzyme evolution, transferase
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27113.00

構造登録者

Perez, M.,Munoz, S.,Cea, P.,Castro-Fernandez, V. (登録日: 2023-02-02, 公開日: 2024-02-07, 最終更新日: 2024-10-23)

主引用文献

Cea, P.A.,Perez, M.,Herrera, S.M.,Munoz, S.M.,Fuentes-Ugarte, N.,Coche-Miranda, J.,Maturana, P.,Guixe, V.,Castro-Fernandez, V.
Deciphering Structural Traits for Thermal and Kinetic Stability across Protein Family Evolution through Ancestral Sequence Reconstruction.
Mol.Biol.Evol., 41:-, 2024

PubMed Abstract: Natural proteins are frequently marginally stable, and an increase in environmental temperature can easily lead to unfolding. As a result, protein engineering to improve protein stability is an area of intensive research. Nonetheless, since there is usually a high degree of structural homology between proteins from thermophilic organisms and their mesophilic counterparts, the identification of structural determinants for thermoadaptation is challenging. Moreover, in many cases, it has become clear that the success of stabilization strategies is often dependent on the evolutionary history of a protein family. In the last few years, the use of ancestral sequence reconstruction (ASR) as a tool for elucidation of the evolutionary history of functional traits of a protein family has gained strength. Here, we used ASR to trace the evolutionary pathways between mesophilic and thermophilic kinases that participate in the biosynthetic pathway of vitamin B1 in bacteria. By combining biophysics approaches, X-ray crystallography, and molecular dynamics simulations, we found that the thermal stability of these enzymes correlates with their kinetic stability, where the highest thermal/kinetic stability is given by an increase in small hydrophobic amino acids that allow a higher number of interatomic hydrophobic contacts, making this type of interaction the main support for stability in this protein architecture. The results highlight the potential benefits of using ASR to explore the evolutionary history of protein sequence and structure to identify traits responsible for the kinetic and thermal stability of any protein architecture.

PubMed: 38913681
DOI: 10.1093/molbev/msae127

実験手法

X-RAY DIFFRACTION (2.7 Å)