Metalloenzyme-catalyzed oxidations of nitric oxide in biosynthesis and nitrosative stress protection

Jonathan D. Caranto, Sarah Jennings, Christopher Martin, Ashley Holland, Zhongxin Ma, Manyun Chen, Victor Davidson, Yousong Ding

University of Central Florida, University of Florida

Metalloproteins catalyze nitric oxide (NO) chemistries in bioenergetics pathways, natural product biosynthesis pathways, and to protect against cell damage caused by nitrosative stress. Our lab is interested in the mechanisms of oxidative NO-dependent metalloenzymes involved in natural product biosynthesis and nitrosative stress protection. Understanding the mechanisms of these enzymes will enable the engineering of nitration biocatalysts and provide insight into how human pathogens evade the human immune response. The presentation will discuss TxtE, a cytochrome P450 (CYP) homolog that mediates a nitric oxide (NO)-dependent direct nitration of tryptophan (Trp) to form 4-nitrotryptophan (4-NO₂-Trp), and a hemerythrin-like protein (HLP) found in pathogenic Mycobacteria. Both enzymes oxidize NO to either perform nitration or to detoxify it by producing nitrite or nitrate. Our most recent working elucidating the mechanisms and structure-function relationships of these enzymes will be discussed.