Work

Snapshots of Motion: A Novel Structural Intermediate Reveals Conserved Dynamics in Archaeal DNA Ligases

Year: 2026

Type: article

Abstract: ABSTRACT We present the first x‐ray crystallographic structural evidence of an archaeal DNA ligase showing the AMP covalent adduct together with further cofactor hydrolysis, capturing a transient intermediary in the first step of the ligation reaction, triggered by the pyrophosphate hydrolysis. Our crystallographic models of Thermococcus gammatolerans DNA ligase (LigTgam), coupled with bioinformatic analysis of at least 28 crystallographic structures from ATP‐ and NAD + ‐dependent DNA ligases, highlight the central role of domain mobility. Notably, elevated B ‐values are consistently observed in key catalytic and binding regions, suggesting a link between structural flexibility and enzymatic efficiency. Remarkably, this pattern of high B ‐values is conserved in replicative ligases, including bacterial Lig A, indicating a broader evolutionary relevance. These fluctuations emphasize the importance of conformational adaptability in accommodating substrate DNA and facilitating catalytic steps, including adenylation and phosphodiester bond formation. In this work, we delve deeper into this dynamic behavior, providing evidence of its critical role in ligase function.

Source: Proteins Structure Function and Bioinformatics

DOI: 10.1002/prot.70116

Authors: A. X. Quintana‐Armas, E. Flores‐Hernández, C. Cardona‐Félix, E. Rudiño‐Piñera

Institutions: Universidad Nacional Autónoma de México, Centro de Investigaciones Biológicas del Noroeste S.C.

Language: English

Topic: Enzyme Structure and Function

Subfield: Materials Chemistry

Field: Materials Science

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $4,550

Funders: Consejo Nacional de Ciencia y Tecnología, Université Paris-Sud, Sistema Nacional de Investigadores, Institute of Genetics