9OAV

TNA polymerase, 8-64, binary complex

9OAV の概要

• エントリーDOI: 10.2210/pdb9oav/pdb
• 分子名称: 8-64, TNA polymerase, Template, Primer, ... (5 entities in total)
• 機能のキーワード: enzyme engineering, b-family polymerase, tna polymerase, polymerase, binary complex, transferase, transferase-dna complex, transferase/dna
• 由来する生物種: Thermococcus kodakarensis; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 99572.30

構造登録者

Lee, J.J.,Maola, V.A.,Chim, N.,Chaput, J.C. (登録日: 2025-04-21, 公開日: 2025-12-10, 最終更新日: 2025-12-31)

主引用文献

Hajjar, M.,Maola, V.A.,Lee, J.J.,Holguin, M.J.,Quijano, R.N.,Nguyen, K.K.,Ho, K.L.,Medina, J.V.,Botello-Cornejo, E.,Barpuzary, B.,Chim, N.,Chaput, J.C.
Directed evolution of a TNA polymerase identifies independent paths to fidelity and catalysis.
Nat Commun, 2025

PubMed Abstract: Directed evolution facilitates functional adaptations through stepwise changes in sequence that alter protein structure. While most campaigns yield solutions that maintain the framework of a rigid protein architecture, a few have produced enzymes with more notable structural differences. One example is a polymerase that was evolved to synthesize threose nucleic acid (TNA) with near-natural activity. Understanding how this enzyme arose provides a model for studying pathways that guide enzymes toward more productive regions of the fitness landscape. Here, we trace the evolutionary trajectory of an unnatural polymerase by solving crystal structures of key intermediates along the pathway and evaluating their biochemical activity. Contrary to the view that fidelity is a product of increased catalytic efficiency, we find that accuracy and catalysis are decoupled activities guided by separate ground-state and transition-state discrimination events. Together, these results offer a glimpse into the forces responsible for shaping the emergence of new enzyme functions.

PubMed: 41413390
DOI: 10.1038/s41467-025-67652-1

実験手法

X-RAY DIFFRACTION (2.5 Å)