Stanford study shows how modifying enzymes’ electric fields boosts their speed

A seemingly subtle swap of metals—substituting a zinc ion with a cobalt ion—and a mutation ramps up the overall electric field strength at the active site of an enzyme, Stanford scientists find. The result is a predictably modified enzyme that works an astonishing 50 times faster than its unmodified analog.

Stanford researchers have demonstrated a way to dramatically speed up the reaction rate of an enzyme, a finding that could pave the way to designing ultra-fast synthetic enzymes for a range of industrial and medical uses.

Honed over billions of years of evolution, biological enzymes are marvels of chemistry. These specialized proteins serve as catalysts for accelerating chemical reactions essential to life as well as processes used in the food, pharmaceutical, and cosmetic industries.    

Ever since enzymes’ discovery nearly two centuries ago, scientists have sought ways to make them even faster. Most fabricated enzymes, though, have failed to match the lofty efficiency standards of nature-made varieties. And even where some successes have been realized through directed evolution, a protein engineering method that mirrors nature’s trial-and-error approach, these successes so far have been by chance, not because of a deeper understanding of how enzymes work or could be modified to work more swiftly.

Now, in a new study, researchers at Stanford’s School of Humanities and Sciences and SLAC National Accelerator Laboratory have debuted a modified enzyme that works an astonishing 50 times faster than its unmodified analog. The findings derive from pioneering research at the university regarding electric fields generated at “active sites,” the pocketlike places where revved up chemical reactions occur. Based on this concept, the researchers tweaked the chemistry of the active site, boosting its electric field strength and specificity to deliver the zippy results.  

Read more on Stanford University website

Image: X-ray crystallography was used to investigate and compare the 3D crystal structures of the unmodified enzyme containing an ion of zinc (Zn) (pictured left) and the modified enzyme with a cobalt (Co) ion in place of zinc (pictured right).