Prof. Steven Boxer discovers the role of electrostatics in enzymes.
Enzymes have revolutionized the fields of chemical and biological engineering. These catalysts are not only responsible for our biological existence, their catalytic and selectivity have led to new industrial processes, products, medicines and much more. In fact, enzymes have the ability to speed up a reaction that would typically take billions of years by 25 orders of magnitude.
Unfortunately enzymes are not cheap or well understood, and replacing enzymes with cheaper yet equivalent catalysts has been a challenge. Even replicating an enzyme with an atomic blueprint has met with limited success. However, Professor Steven Boxer from Stanford University has discovered that the majority of an enzyme’s feats are attributed to its electrostatic fields.
"Clearly it's important to have the right pieces in place, but there seems to be something more," said Boxer. "There are a lot of really strong opinions about this, but one idea that's emerged, mostly from simulations, is that electrostatic interactions within the enzyme might play an important role lowering the barrier for the reaction, but we haven't had a way to measure this until now."
What is known about the enzymatic process it that the proteins bind to a substrate at the active site. The enzyme then works to form and break bonds by a step-by-step transfer of electrical charges. Many theorized that the electrostatic field of the enzyme lowers the barrier of reaction.
Ketosteroid isomerase homodimer's structure which is based on a PyMOL rendering of PDB 3VSY. Source Ohamto.
Boxer’s team was able to probe the active sites of the enzyme ketosteroid isomerase (KSI) in its natural form, and “mutants” with altered active sites. The findings saw that the natural KSI enzyme produced a large electric field on the substrate that increased the rate of reaction. When the natural KSI and the mutants were compared, it was found that the electrostatic field was responsible for 70% of the enzyme’s performance.
Boxer said, "The reality is that it was never going to be all one thing or another, but 70 percent is a very significant contribution, and these experiments tell us that the electrostatic field is directly impacting the rate in this case … This shows that the electrostatic field lowers the barrier to reaction, and is really the key to catalysis in this enzyme."
Boxer suspects that the electrostatic effect is consistent with other enzymes, but the contribution will vary. Therefore, by assessing these electrostatic fields the world’s chemists, chemical engineers and biological engineers might be able to increase the efficiency of enzymes, design new enzymes or even design chemical catalysts to increase the electrostatic field.
Boxer mentioned that, "This work is basic science, and on its own is not going to solve the energy crisis or anything like that … But it will help us to better interpret a lot of good data that's already out there, and in the broader sense this will help us understand what's so unique about enzymes based on fundamental physical concepts."