Professor Elliott Published in Nature Communications: Enzymatic Discovery Cools a ‘Hot’ Intermediary

in Elliott, Sean, Front Page, Grants, NIH, Publications, Recognition, Research
March 7th, 2019

Enzymatic Discovery Cools a ‘Hot’ Intermediary

In the world around us enzymes perform the wizardry of allowing reactions that should occur, to do so in a timely fashion. Enzymes that transform hydrogen peroxide often generate a highly reactive, ‘hot’ intermediate along the way, which will transform another molecule in a startling feat of chemistry. In a recent research study a team from Boston University, MIT and Carnegie Mellon University has found that one such reactant generated by a bacterial enzyme can be ‘cooler’ than thought previously.

In the March 7, 2019, Nature Communications report, the team has discovered a new class of peroxide-transforming enzyme that is found widely in bacterial organisms. Through their studies of one family member, called BthA, they have learned that the ‘hot’ intermediates produced by enzymes like BthA have diverse properties, which will hopefully lead to further discoveries in biological chemistry.

Enzymes like BthA are referred to as diheme peroxidases, which make use of two natural heme iron cofactors that talk to each other, in terms of how they share their own electrons. Previous studies have found that enzymes like BthA produce highly reactive states where both irons share electron via pathway provided by a conserved amino acid residue, called Tryptophan. 

By combining methods of biochemistry, electrochemisty and spectroscopy, Kimberly Rizzolo and Prof. Sean Elliott (Boston University) worked with Andrew Weitz and Prof. Michael Hendrich (CMU) using Electron Paramagnetic Resonance and Mössbauer spectroscopies in order to demonstrate that BthA would produce the same fierce oxidant that has been reported. Stunningly, they found that the ‘hot’ state persists for over an hour, instead of rapidly quenching like something reactive should.

Extending these efforts with X-ray crystallography, the BU team paired with Steve Cohen and Prof. Catherine L. Drennan (MIT/HHMI) to solve the structure of BthA. Through that molecular view,, it is clear that Nature has changed the way in which the two heme irons of BthA talk to one another, substituting the native Tryptophan for a different amino acid residue. That change lets the chemical equivalent of napalm persist in the enzyme, until it is quenched.

“The work illustrates how if we look at the microbial world, enzyme continue to surprise us with how inventive they can be with chemical transformations,” says Sean Elliott. “If we can understanding the wiring, we’ll be able to re-wire these catalysts to do the reactions we need them for.”

Further Information:  The research was funded by the National Institutes for Health (National Institute for General Medical Sciences), the Howard Hughes Medical Institute, the Canadian Institute for Advanced Research, and the Department of Energy.

CONTACT INFORMATION:  Sean J. Elliott, elliott @ bu.edu, 617-358-2816, Boston University.

PUBLICATION: Rizzolo K, Cohen SE, Weitz AC, López Muñoz MM, Hendrich MP, Drennan CL, Elliott SJ.  A widely distributed diheme enzyme from Burkholderia that displays an atypically stable bis-Fe(IV) state”, Nature Communications, 7 March, 2019. DOI: 10.1038/s41467-019-09020-4.

EMBARGO INFORMATION: The manuscript is currently under embargo by Nature Communications, the publication date is 7 March 2019.

PUBLICATION LINK: https://www.nature.com/articles/s41467-019-09020-4