NIH Reporter #5R35GM147515-05

Mechanisms of novel biological nitrogen chemistries

Research project funded by NIGMS to study enzymatic nitric oxide-dependent reactions with implications for disease understanding and therapeutic enzyme engineering.

Description

The proposed research will study enzymatic reactions that catalyze nitric oxide-dependent reactions. These enzymes will help understand the onset of neurodegenerative diseases, antibiotic biosynthesis by bacteria, and how infectious bacteria survive the human immune response. In addition, this work will enable the engineering of enzymes to make synthesis of human therapeutics less costly, more efficient, and less harmful to the environment. The research focuses on mechanisms and structure-function relationships of nitric oxide (NO)-dependent enzymatic activities relevant to protein nitration, natural product biosynthesis, and nitrosative stress protection in pathogenic bacteria. It includes studying metal-catalyzed nitration pathways, cytochromes P450 (CYPs) such as TxtE, and metalloenzymes involved in Mycobacterial virulence like hemerythrin-like proteins (HLPs). The project aims to discover novel nitrogen biochemistries, pursue enzyme engineering, and establish a training program in mechanistic metalloenzymology and natural product biosynthesis.

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