Scientists finally got a sharp look at SacC, the bacterial enzyme that builds the molecular core of trabectedin, a drug used to treat soft tissue sarcoma. Using cryo-electron microscopy and clever chemistry, researchers from the University of Tokyo and Tohoku University captured near-atomic-level images of the enzyme in action. The breakthrough could pave the way for optimizing existing cancer drugs and engineering entirely new ones.
Scientists have achieved something that's been frustratingly out of reach — a near-atomic-resolution image of SacC, the bacterial enzyme responsible for assembling the complex five-ring molecular core of safracin B. That core structure is shared with trabectedin, a chemotherapy drug used to treat soft tissue sarcoma. The research, published in the Journal of the American Chemical Society, was led by teams from the University of Tokyo and Tohoku University.
The challenge? SacC is a shape-shifter. It moves dramatically as it works, and it tends to clump in solution — both of which make imaging a nightmare. The team tackled this on two fronts: chemists synthesized small molecules that mimic the enzyme's intermediate states, while structural biologists discovered that a tiny partner protein, SacE, dramatically stabilized the enzyme. With the sample behaving, they flash-froze it and imaged it via cryo-electron microscopy, reconstructing a 3D model from thousands of individual snapshots.
Key Takeaways:
Why it matters: Understanding exactly how nature builds complex drug scaffolds could help researchers optimize existing therapies and design new ones — potentially transforming how cancer drugs are developed.
