Friday, March 5 at 4:00pmVirtual Event
"Taking a Bath: Discovery and Serendipity in Metalloenzymology"
ABSTRACT: A major challenge facing the fields of bioinorganic chemistry and mechanistic enzymology is the ability to parse the overwhelming sequence data that is available from microbial genomes. Such data can give new insights into the biological world around and within us (e.g., the human microbiome, or the geochemical cycles). For a chemist, such data provides a new treasure trove of biological sequence space that includes new, undiscovered enzymes. Here, the approach of using sequence similarity networks as a bioinformatic tool will be presented to make predictions of novel reactivities, using the case study of heme-based enzymes of the ‘bacterial cytochrome c peroxidase’ superfamily. So-called ‘bCCPs’ are heme enzymes that typically reduce hydrogen peroxide to water, as part of detoxification system in the native organism. All bCCPs contain two heme cofactors, one that serves as an active site for oxidant reactivity, and other as a means of long-range electron transfer. Yet, the bCCP called “MauG” is associated with using either hydrogen peroxide or oxygen as an oxidant, to oxidatively install a C-C bond in the far-away residues of the precursor protein of methylamine dehydrogenases. How does the same protein fold, and the set of redox active heme cofactors achieve such diverse chemistry? Here, the SSN approach reveals that the bCCP_MauG superfamily is much more diverse than previously thought, including a link to novel enzyme found widely in Burkholderia microbes, which we term BthA. The structure-function relationships of BthA will be described, including surprises in the environment around and between the heme cofactors.
BIO: Sean Elliott grew up in Tucson, AZ, but traded blazing sun for changing leaves as he received his BA in English and Chemistry at Amherst College, summa cum laude. He conducted his graduate studies in Chemistry at Caltech, receiving a Ph.D. in Bioinorganic Chemistry in 2000. He followed that with time as an EMBO Long-term Postdoctoral Fellow at the University of Oxford, Inorganic Chemistry Laboratory. He started his independent career as an Assistant Professor of Chemistry at Boston University in 2002, was promoted to Associate Prof in 2008, and Full Professor in 2014. He is currently Director of Graduate Studies at Boston University, and a founding member of BU-GLIDE, a Chemistry group listening on inclusion, diversity and equity. He has received an NSF-CAREER award, multiple Research Corporation Scialog Awards, and awards from Boston University for teaching and mentoring. He has a wife and daughter (aged 12) and a labradoodle named Casey. He was sorted in Ravenclaw, but chose Gryffindor.