2023 Volume 66 Issue 12 Pages 689-694
Cryo-electron microscopy (cryo-EM) has become a powerful tool for structural analysis, owing to the recent “resolution revolution” and currently it is the mainstream technique for analyzing the structures of large molecules. The three-dimensional structural information of proteins is indispensable for structure-based drug design, particularly in the field of drug discovery.
Hear we presents what information can be retrieved from single-particle analysis by cryo-EM, using the recently identified Na＋-pumping NADH-Quinone oxidoreductase as an example. The structural analysis of the protein determined the overall structure at 2.9 Å resolution and identified the cofactors within it, which revealed the mechanism of electron transfer. Furthermore, flexible conformational changes were successfully visualized, suggesting the possibility of conformational changes associated with electron transfer. These findings demonstrate the utility of cryo-EM for structural analysis, highlighting its transformative potential in the field of drug development, particularly in understanding the mechanisms of large molecular complexes.
