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Nitin Jain Publishes in PNAS

A paper, Entropic contribution to enhanced thermal stability in the thermostable P450 CYP119, from the laboratory of Dr. Nitin Jain has been accepted for publication in the prestigious journal Proceedings of the National Academy of Sciences of the United States (PNAS). An undergraduate student, Sara Lemmonds, who recently graduated from the BCMB department, is a co-first author on this paper. The Jain investigates a family of enzymes called Cytochrome P450s, that are of high pharmaceutical relevance since they play a major role in metabolism of > 90% of medicinal drugs within our body and are thus very important targets for drug design. Interestingly, these enzymes are also found in bacteria that are able to survive under extreme environments such as hot springs or volcanic deposits, where they are observed to function normally under the hot conditions. Thus, there is considerable interest in understanding what makes these enzymes withstand heat without falling apart, so that they can be manipulated and exploited as efficient catalysts in the biotechnology and chemical industry where high temperatures make reactions to manufacture new medical and chemical products possible at lower costs. Proteins that are stable to heat are generally thought to be very rigid entities to maintain their heat stability. However, research in the Jain lab with the thermostable P450 enzymes brings this notion into question. They show with various cutting-edge spectroscopic methods that thermostable proteins can actually be quite flexible and use this flexibility to disperse the heat very efficiently throughout the protein using entropic means. These experiments also reveal that some of this flexibility is additionally utilized in making the enzymes increasingly active in catalyzing reactions at high temperatures. Their findings on the flexible nature of these enzymes now opens up new avenues for engineering novel P450 enzymes for use as catalysts at high temperatures for applications ranging from manufacturing drugs for diseases such as cancer, arthritis, anxiety disorders, allergies, infections and heart conditions to making novel chemicals, cosmetics, dyes and environmental bioremediation via microbial methods.

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