A team of Michigan State University scientists using a new cooling method they created – have uncovered the inner workings of a key iron-containing enzyme1(酶) , a discovery that could help researchers develop new medicines or understand how enzymes2 repair DNA3. Taurine/alpha-ketoglutarate(酮戊二酸) dioxygenase(加双氧酶) , known as TauD, is a bacterial4(细菌的) enzyme that is important in metabolism5(新陈代谢) . Enzymes in this family repair DNA, sense oxygen and help produce antibiotics6(抗生素) .
Specifically, the MSU team was interested in how iron and oxygen atoms reacted together in the enzyme. Understanding how TauD works, which serves as a model for many other proteins, has implications in the scientific and medical fields, said Robert Hausinger, MSU professor of microbiology and molecular7 genetics.
"This is a broad enzyme family with similar mechanisms," he said. "Understanding how TauD works sheds light on how many other enzymes function from bacteria to humans. This can be applicable to a wide variety of essential enzymes of medical and agricultural interest."
For example, Hausinger said, understanding how the enzyme works can help scientists design inhibitors to prevent it from doing its job, which is a key step in preventing diseases. Also, understanding how the iron inserts oxygen atoms into other molecules8(分子,微粒) provides insight into how enzymes metabolize the majority of medical drugs or environmental pollutants9(污染物) in the human body.
As understanding how enzymes work can be very complicated — such reactions often are complex, fast and require multiple steps — the MSU team developed a new method to follow the TauD reaction. The difficult part for researchers was to slow down the reaction enough that the individual steps can be observed; one way to slow down an enzymatic10 reaction is to cool it.
The team used a stream of cold nitrogen(氮) gas to slow down the reaction at -36 C (-33 F). To prevent freezing and to keep the reaction going, the scientists used ethylene glycol(乙烯乙二醇) – the same antifreeze(防冻剂) that goes in vehicles.
Once the reaction started, the team used lasers – in an advanced method called Raman spectroscopy(拉曼光谱学) – to follow the vibrations11 of iron and oxygen atoms in TauD to determine how the reaction progressed. They found never seen before steps in the TauD reaction, overturning conventional thought.