“New approaches in millisecond-scale time-resolved crystallography technique for 3D structural and dynamic studies of enzymes of therapeutic interest”
 

This project investigates how structural dynamics in enzymes facilitate efficient catalysis of complex biochemical reactions. Using time-resolved serial crystallography at X-ray free-electron lasers (XFELs) and synchrotrons, the research will capture transient intermediates with atomic resolution to understand how enzymes navigate the reaction coordinate. Molecular simulations, including hybrid quantum mechanics/molecular mechanics and molecular dynamics, will complement experimental data to reveal fundamental reaction mechanisms in enzymes such as AnmK, AGT, CYP2D6, and RFK-PNPOx. The project aims to create molecular movies of enzymatic reactions, offering insights into enzyme function, evolution, and potential drug design strategies. Ultimately, these findings could impact biotechnology and medicine by improving our ability to engineer artificial biocatalysts and develop targeted therapies.
 

Reference: PID2023-151100NB-I00.
 

Participating Institutions: CSIC, UGR, BIFI
 

Start and End dates: 09/01/2024 - 31/12/2027.
 

PI: José M. Martín García
 

Funding Agency: