Photo: Professor Bernie Kraatz, U of T Scarborough Vice-Principal Research

Written by Don Campbell

The research, authored by Professor Bernie Kraatz and PhD student Annaleizle Ferranco, discovered a way to chemically generate small molecular models that contain an amino acid called histidine that plays a critical role in the structure of proteins and enzymes in the body as well as how they work.

“Studying metal-containing enzymes like zinc with a high level of precision can be extremely difficult,” says Kraatz, who specializes in creating new materials to detect biomolecules in the body.

“This is where small models come into play.” 

The main benefit of the models developed by Kraatz and his team is that they can lead to a better understanding of how zinc enzymes actually work. (Enzymes are molecules that act as a catalyst for biochemical reactions, while proteins are large complex molecules that perform many different functions.)

There are literally hundreds of zinc proteins in the body responsible for many important biological functions like controlling blood pH—an imbalance of which can lead to serious health problems—to even those that interact with our DNA. It’s even been suggested that too much zinc may lead to various neurodegenerative diseases, such as Alzheimer’s.

“These proteins control some critically important functions in cellular organisms, including humans, so it’s important to know how they really work,” says Kraatz.

In order to gain a better understanding of how they work, researchers need to study in greater detail histidine-zinc interactions, the structure and arrangement of amino acids around zinc and how they influence processes during catalytic transformations. When it comes to proteins, the zinc binding site that is of interest to researchers is often found deep within the protein, making it very difficult to study the metal-based transformations that take place. 

“Since proteins are much larger and more complex, it’s often difficult to get the detailed information necessary to truly understand the role of the catalytic metal site,” says Kraatz.

Ferranco was able to design the models by first chemically constructing them out of smaller molecules, and then by constructing the metal binding sites. Kraatz likens the process to building with Lego blocks where they can create a variety of new geometric shapes while also controlling its structure.

The research, which was supported by a grant from the Natural Sciences and Engineering Research Council of Canada (NSERC), is published in the journal Dalton Transactions.

Kraatz says the next step for the research is to see how the molecular models perform in real life conditions like controlling pH levels in the blood, among others.