Decoding protein dynamicity in DNA ligase activity through deep learning-based structural ensembles.

ABSTRACT: Numerous proteins perform their functions by transitioning between various structures. Understanding the conformational ensembles associated with these states is essential for uncovering crucial mechanistic aspects that regulate protein function. In this study, we utilized AlphaFold3 (AF3) to investigate the structural dynamics and mechanisms of enzymes involved in DNA homeostasis, using NAD-dependent Taq ligases and human DNA Ligase 1 as a case example. Modifying the input parameters for AF3 yielded detailed conformational states of a DNA-binding enzyme, thereby offering enhanced mechanistic insights. We applied AF3 to model the various stages of thermophilic Taq DNA ligase activity, from its ground state to substrate-bound complexes, revealing significant mobility in the N-termina

SUBMITTER: Mishra N 

PROVIDER: S-EPMC11581005 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature