Professor Elliott Published in Nature Communications: Enzymatic Discovery Cools a ‘Hot’ Intermediary
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
BU Chemistry is pleased to announce a three-year renewal of funding for our NSF Research Experiences for Undergraduates (REU) Program. This summer program, hosted by the Chemistry Department, provides students from primarily undergraduate institutions with opportunities to work in advanced research laboratories. Of the 33 students who participated in the program over the past three years, 91% came from underrepresented minority groups, better than 60% were women, and almost 45% came from community colleges. Many of them co-authored peer-reviewed publications, presented their findings at conferences, and/or decided to attend graduate school, including BU. Another measure of the program’s success is its ever-expanding pool of applicants, with over 600 applications received for the summer 2018 program alone.
Chemistry would like to give special recognition to the efforts of Professors Linda Doerrer, Principal Investigator (PI), and ,John Snyder, co-PI, and Chemistry Departments Proposal Development Administrator Daniel Hauck, whose hard work and commitment to the program made this renewal possible.
Due to a change in the National Science Foundation’s funding periods, the Chemistry Department will not be hosting REU students for the Summer of 2019. The program will be active again in the Summer 2020. For more information, including the application process, visit the BU Chemistry REU.
We are excited to announce that the Boston University Chemistry Department’s newest faculty member, Professor Maria Kamenetska, was recently awarded an Air Force Young Investigator Research Program Grant (AFOSR-YIP) for her novel work on robust DNA conductance and force signatures for detecting protein binding to DNA with base-pair resolution.
With the creation of the BU HUB educational requirements, Boston University has committed to a fully integrated and interdisciplinary approach to higher education. Dr. Kamenetska, who goes by Masha, holds a joint appointment between the Chemistry and Physics departments and is also a member of our Materials Science & Engineering Department. Masha’s joint appointment and her truly interdisciplinary research are an excellent example of BU’s commitment to educational integration.
The AFOSR-YIP funded project, which will support her work and that of 2 graduate students, focuses on using DNA conductivity as a sensor for DNA-protein interactions. The innovative research will first investigate the degree of electron transfer as a function of binding conformation of DNA between metal electrodes to help address some of the debates in the literature regarding electron transport in DNA. She and her research group will use this information to correlate the specific ways that DNA constructs bind in the junction and conduct current, which will create a unique conductance signature of various conformations of the DNA molecule in the junction; this will allow her and her research group to probe protein binding to specific base-pairs of that molecule. The application of this technique will be used to investigate the basic unit of Chromatin—known as the nucleosome—which controls the access of DNA for transcription and thus plays a key role in gene regulation.
Dr. Kamenetska says this about the award and the project “I am grateful to the Air Force Office of Scientific Research for this opportunity. With their support, I look forward to developing a deeper understanding of electron transport properties of DNA and using this knowledge to establish novel single molecule techniques for probing structure-function relationships in biology and material science.”
We were pleased to announce the Department of Chemistry student award winners for the 2017-2018 academic year at the Orientation BBQ. For those who may have missed it, here are the award winners.
Sugata Ray Memorial Award for International Students: Nathchar Naowarojna (Liu Lab)
This award was established by the Ray family in memory of their son, Sugata Ray, a former graduate student in the Chemistry Department, to recognize an international Ph.D. candidate each year who excels in his or her graduate studies. Research, academic performance, teaching, and service contributions to the Department are all considered in selection of the awardee.
Professor Liu writes, "Can has demonstrated her potential to thrive in the academic environment and greatly contribute to the field of natural product biosynthesis and enzymology. Her skills and knowledge in research, and dedication to mentorship make her an exceptionally qualified nominee.” She has authored or contributed to an impressive number of publications, and demonstrates an extraordinary commitment to undergraduate mentoring through her teaching assignments and undergraduate research supervising.
Lichtin Award for Research: David Stelter (Keyes)
This award was established in honor of Norman Lichtin, a distinguished research scientist and former Chair of the Chemistry Department. The award recognizes students that are distinguished by their exceptional contributions to chemical research in their doctoral studies.
Professor Keyes writes, “David is a wonderful student, one of my best ever. Despite having to teach almost full time he has achieved significant research results, and never lost his enthusiasm, while also being a joy to have as a TF.” David is first author on two papers, contributed to two more, and has a large body of results to write up and exciting work in progress.
Feldman Award: Lindsey Walker (Elliott Lab)
The Feldman Fund was established by the Feldman family to memorialize Julius Feldman, who served for many years as Associate Chairman of the Chemistry Department and who took a special interest in the welfare of graduate students. The Feldman Award recognizes outstanding accomplishments in research, teaching or service.
Lindsey is a fifth year student in the Elliott Lab who has not only made significant and impressive research contributions but is a great communicator of science, and stands out as an excellent leader.
Professor Elliott writes, “Lindsey is a sharp, devoted, creative and highly driven student, who is well on her way to being a successful scientific leader. She is a talented researcher who is motivated by a concern for the environment, and a desire to use electrochemistry as a functional tool to improve society. She is a wonderful student, and I am very lucky to have her in my lab.”
Departmental Award for Outstanding Graduate Student Research: Lauren Viarengo (Whitty Lab)
Professor Whitty writes, "Lauren has a strong intellect and is exceptionally diligent and conscientious in everything she does. Lauren is also highly sought after as a Teaching Fellow, being very conscientious and having excellent interpersonal and communication skills. But what really sets her apart is her fearlessness in taking on new research challenges, and her exceptional drive. I believe she serves as an example of everything we look for in our very best graduate students, and is an ideal candidate for a graduate student award to recognize her extraordinary capabilities and efforts."
Congratulations to all of our award winners!
As they finished out the sixth and final week of the 2018 GROW (Greater Boston Research Opportunities for Young Women) program, the 12 summer interns present their capstone to the six weeks of research conducted during a Poster Session held on Friday, August 10th in the Science Metcalf Building Lounge located on the first floor from 2:00 – 4:00 PM.
LERNet was created in 1998 to provide programming for K-12 students interested in pursuing the STEM fields and to encourage teacher development. In recent years, Brossman says, she has become more focused on young women, because they face a gender imbalance in STEM fields. The GROW program came into being this year after Deborah Perlstein, a CAS assistant professor of chemistry, came to Brossman looking for ways to broaden the impact of a research project so that it would satisfy a National Science Foundation (NSF) grant requirement. After her project was funded for one student, they decided to go further.
“For young women interested in careers in math and science, it’s really important for them to have an opportunity to get in lab and see what that’s like,” says Perlstein. “It’s also important for them to have the opportunity to see some (female) role models. That was important to me in choosing my career path.
”Brossman and Perlstein put together a program with funding from sources including Vertex, Pfizer, and other companies; LERNet; the chemistry and biology departments; CAS; BU’s ARROWS (Advance, Recruit, Retain & Organize Women in STEM); and existing NSF grants, all adding up to about $30,000. Despite a late posting of the application, in April, some 60 rising juniors and seniors from Greater Boston high schools applied. A dozen students were placed in BU chemistry and biology labs and assigned research projects and graduate student or post-doc mentors.
“I wanted to create an accessible program for local students who may not be able to afford some of the existing programs or who needed to work during the summer,” Brossman says. “We wanted to give the students a stipend so we could eliminate any financial barriers to participation.”
Here are some photos from this years Poster Session:
On Friday, May 4th, 2018 the work of 22 students was spotlighted in this year’s Undergraduate Research Symposium (URS). The high-caliber projects presented underscored the importance of the hands-on, challenging research that is the hallmark of Boston University's Chemistry major. The even was organized by the Undergraduate Programs Committee, Professor John Snyder and coordinated by our Undergraduate Program Coordinator, Julia Jesielowski.
URS was first instituted in 1987 by then Director of Undergraduate Studies, and now Emeritus, Prof. Mort Hoffman, and has been a much anticipated, spring’s-end annual event ever since. The Symposium is modeled along the lines of talks at an American Chemical Society (ACS) meeting: 12 minutes of presentation followed by 3 minutes of questions and discussion. Capping the day was the announcement of the Departmental Awards, followed by a celebratory pizza party for the students, their faculty advisers, graduate mentors, and their guests.
Professor Bjoern Reinhard awarded an NSF-CHE 3 Year grant to Study Plasmon Coupling Correlation Spectroscopy
Prof. Reinhard was recently awarded a 3 Year renewal of her National Science Foundation Division of Chemistry (NSF-CHE) Grant titled: Plasmon Coupling Correlation Spectroscopy. This will help Prof. Reinhard and his research group investigate the unique optical properties and strong field localization properties of plasmonic nanoparticles as they are important components of many chemical sensing technologies and Efield enhanced spectroscopies. The research will advance the field of chemical imaging and sensing by introducing the concept of correlation spectroscopy to localized surface plasmon resonance (LSPR) spectroscopy. The ambitious research plan will utilize distance-dependent near-field coupling between plasmonic nanoparticles that cause spectral fluctuations in the far-field to monitor interparticle separations at signal intensities that are manifold higher than that of conventional dyes. Importantly, due to their superb photophysical stability plasmonic nanoparticles overcome existing limitations of fluorescence based correlation approaches in terms of maximum observation time and will facilitate a continuous signal correlation over a much longer time than is currently possible with fluorescence based approaches entirely without blinking. The research funded by this grant is transformative as it will facilitate the application of optical signal correlation techniques to systems that have, so far, not been accessible with conventional fluorescence-based correlation methods.
Besides the scientific impact, the research project has a series of educational and outreach components as well as detailed plans to encourage the participation of underrepresented groups in science and engineering. The grant will allow for the development of new course work and training opportunities for students from the high-school to graduate school level. Furthermore, Dr. Reinhard will organize annual workshops for students from inner city high schools, which typically have high representations from groups underrepresented in science and engineering. His main goal is to enthuse these students about the research of the proposal and to attract them to a career in STEM fields. The course material developed during the lifetime of the project will be disseminated via the PI’s homepage to further enhance the broader impact of this proposal.
Prof. Doerrer was recently awarded a 3 Year renewal of her National Science Foundation Division of Chemistry (NSF-CHE) Grant titled: Oxidation Catalysis with 3d Complexes Bearing Fluorinated Alkoxide Ligands. This will help Prof. Doerrer and her research group continue their investigation into oxidation catalysis. The project will focus on developing more effective and sustainable catalytic reactions for chemical synthesis, which is critical for the 21st century. Oxidation of C-H bonds remains a central component of chemical transformations with many remaining challenges. This work builds on her recent success with Cu/O2 chemistry that has demonstrated the effectiveness of fluorinated alkoxide ligands to make highly reactive species for oxidizing C-H bonds. Recently her group has demonstrated catalysis with two different systems, and one reaction that differentiates the two systems. Understanding this difference, extending this success to other earth-abundant metals and potentially to water as a reaction medium are the targets of this award. Proven synthetic and characterization methods will be used, augmented by new ideas and some recent discoveries that hint at new and improved conditions for these needed chemical reactions.
We are happy to announce that Associate Professor Linda Doerrer was recently awarded a $110,000, grant titled “Lanthanide-Based Polymerization Catalysts with Water Resistant Ligands” from The American Chemical Society. The funding, which will last for 2 Years, will help Professor Doerrer explore a family of O-donor ligands, both aryloxide and alkoxide, that are heavily fluorinated in order to further the development of more water-tolerant catalysts, which would be a boon to many industrial polymerization reactions.
Congratulations to Dr. Doerrer for this exciting Award!
Melissa Marquez, a second-year graduate student in Professor Deborah Perlstein’s group, has recently received a 2017 NSF Graduate Research Fellowship. She earned a Bachelor of Science in biochemistry with a minor in mathematics from Mount Saint Mary’s University and as an undergraduate conducted research in Dr. Eric Stemp’s lab focusing on DNA-protein cross-linking resulting from oxidative damage to DNA. She was introduced to Boston by participating in Tufts University’s NSF Research Experience for Undergraduates (REU) program in the summer of 2013 and worked in Dr. Mitch McVey’s lab where she focused on determining the lethality stages in Drosophila melanogaster Werner Syndrome exonuclease mutants. Along with chemistry, Melissa enjoys serving others in their journey toward their science aspirations. She is currently a fellow for the BU NSF GK-12 Global Change Initiative (GLACIER) program where she works at Pierce School in Brookline with a 6th grade science teacher, an officer for BU Women in Chemistry, and a co-leader of the BU Graduate Women in Science and Engineering (GWSE) Girls with Goggles club, an outreach program that provides weekly hands-on activities for middle school girls.
Through the support of the NSF, Melissa aims to obtain a greater understanding of how iron cofactors are biosynthesized through the cytosolic iron sulfur cluster assembly (CIA) pathway. This system is responsible for iron sulfur (FeS) cluster biogenesis for proteins found outside of the mitochondria in eukaryotic organisms. Essential processes such as DNA replication and repair, transcription, and translation, are all dependent on at least one FeS cluster containing enzyme. A key question is: how are these DNA metabolizing enzymes, also termed targets, recognized by the CIA pathway? Melissa plans to discern the mechanism of CIA target recognition by investigating Cia2, a vital component of the CIA targeting complex known for executing target identification in the last step of the system. Not only is cluster targeting poorly understood for the CIA pathway, but it is not known how any cluster biogenesis pathway identifies its targets. By examining how targets are recognized, this work can provide a model for how target recognition is executed for other cluster biogenesis systems. Melissa is primarily interested in pursuing a career in which she can simultaneously work on innovative experimentations closely related to therapeutic development and reigniting students’ appreciation for deeper learning and, ultimately, love for science.