{"id":12671,"date":"2019-08-28T15:40:19","date_gmt":"2019-08-28T19:40:19","guid":{"rendered":"https:\/\/biology.mit.edu\/?p=12671"},"modified":"2020-10-28T22:56:54","modified_gmt":"2020-10-29T02:56:54","slug":"forging-a-new-understanding-of-metal-containing-proteins","status":"publish","type":"post","link":"https:\/\/biology.mit.edu\/forging-a-new-understanding-of-metal-containing-proteins\/","title":{"rendered":"Forging a new understanding of metal-containing proteins"},"content":{"rendered":"<p>Raised in a computer-savvy family well-versed in software and information technology, Rohan Jonnalagadda had a strong desire to \u201cdecode\u201d the world around him. But his kind of code, the genetic one, consists of four repeating letters: A, T, C, and G. \u201cJust like a computer runs on software, I wanted to investigate the code behind the molecular hardware that gives rise to life,\u201d he says. Now a sixth-year graduate student in the\u00a0<a href=\"https:\/\/drennan.mit.edu\/\" target=\"_blank\" rel=\"noopener noreferrer\">Drennan lab<\/a>, he works to decrypt the structure of metal-containing proteins, in order to determine the roles they play in vital cellular reactions.<\/p>\n<p>When Jonnalagadda was an undergraduate biochemistry major at the University of California, Berkeley, it became clear to him that the genetic code was more than just a string of letters; it also serves as the blueprint for all the proteins in the entire organism. These proteins fold into complex 3D structures, which ultimately beget function.<\/p>\n<p>At UC Berkeley, he joined a lab studying the iron-containing protein Heme-Nitric Oxide\/Oxygen (H-NOX) that senses nitric oxide gas in bacterial and eukaryotic cells. When H-NOX binds to nitric oxide, it must change its 3D shape in the process. Jonnalagadda used a technique known as X-ray crystallography to freeze H-NOX in various stages of this conformational change\u00a0<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=Jonnalagadda+R+Kuriyan\" target=\"_blank\" rel=\"noopener noreferrer\">to determine<\/a>\u00a0how it binds the gas molecules.<\/p>\n<p>\u201cI think we sometimes ignore the fact that we need trace metals in order to survive,\u201d he says. \u201cI was interested in continuing to think about what different metals could do in the cell. And using metals opens up a whole new world of chemical reactions that you generally don\u2019t learn about in class.\u201dBy the time he graduated and began his PhD at MIT Biology, Jonnalagadda had been using X-ray crystallography for over two years. Today, as a member of <a href=\"https:\/\/biology.mit.edu\/profile\/catherine-drennan\/\">Catherine Drennan<\/a>\u2019s lab, he continues to leverage this same method to parse the structure of additional metal-containing proteins.<\/p>\n<p>In fact, the two projects that he\u2019s devoted most of his time to over the past five years involve reactions that he\u2019d never even heard of before he arrived at MIT. The focus of his first undertaking was the iron-containing enzyme ribonucleotide reductase (RNR), which helps generate deoxyribonucleotides, the building blocks of DNA.<\/p>\n<p>Jonnalagadda aims to understand how this enzyme is regulated to ensure the cell maintains the proper amount of each type of deoxyribonucleotide, in order to properly replicate and repair its genome. If those ratios are incorrect, the cell could experience detrimental stress.<\/p>\n<p>Because the enzyme is regulated differently in humans than it is in bacteria, scientists hope to one day create antibiotics that target the bacterial RNR while leaving the human RNR unscathed. Jonnalagadda works with the human version, devising an assay that will allow him to better assess the differences between the two enzymes. RNR is notoriously difficult to work with, and so Jonnalagadda has spent much of his time developing ways to purify it so it remains stable.<\/p>\n<p>His second project is a collaboration with researchers at his alma mater, UC Berkeley, investigating isonitriles \u2014 compounds containing a carbon atom tripled bonded to a nitrogen atom. Because isonitriles are used to make drugs like antibiotics, scientists have a keen interest in exploring new ways to produce them. The team discovered that one bacterium,\u00a0<em>Streptomyces coeruleorubidus<\/em>, had a novel and mysterious way of synthesizing these compounds. Jonnalagadda wants to know exactly how these particular bacteria do it.<\/p>\n<p>He is using X-ray crystallography to determine the structure of the iron-containing enzyme ScoE in\u00a0<em>S. coeruleorubidus<\/em><em>,<\/em>\u00a0which is responsible for forming the carbon-nitrogen triple bond characteristic of isonitriles.<\/p>\n<p>\u201cIt\u2019s exciting to be working on a protein that\u2019s only just been discovered,\u201d he says. \u201cThere\u2019s just so much more to learn about its fundamental biological function. I think that\u2019s why basic research is so appealing to me; you never know where the work will take you, or the impacts it could have on human health later on.\u201d<\/p>\n<p>Extending the frontiers of any discipline requires some guesswork and metaphorical bushwhacking, and Jonnalagadda has learned almost as much from his failed experiments as he has from his successful ones. \u201cI\u2019m proud that I\u2019ve been able to use what I\u2019ve learned about experimental design to help others in my lab when they have questions,\u201d he says.<\/p>\n<p>As he considers life post-graduation, he hopes to use the biochemical and structural techniques he\u2019s mastered over the years to secure a job in industry.<\/p>\n<p>\u201cBeing part of a department with such broad and wide-ranging research interests has made it easy to see that my work doesn\u2019t exist in a vacuum,\u201d he says. \u201cIt connects to many different aspects of biology.\u201d<\/p>\n<h5>Photo credit: Raleigh McElvery<br \/>\nPosted 8.23.19<\/h5>\n","protected":false},"excerpt":{"rendered":"<p>Raised in a computer-savvy family well-versed in software and information technology, Rohan Jonnalagadda had a strong desire to \u201cdecode\u201d the world around him. But his kind of code, the genetic one, consists of four repeating letters: A, T, C, and G. \u201cJust like a computer runs on software, I wanted to investigate the code behind [&hellip;]<\/p>\n","protected":false},"author":16,"featured_media":12594,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-12671","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","placement-placement-homepage","research-area-biochemistry-biophysics-and-structural-biology"],"acf":[],"yoast_head":"\n<title>Forging a new understanding of metal-containing proteins - MIT Department of Biology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/biology.mit.edu\/forging-a-new-understanding-of-metal-containing-proteins\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Forging a new understanding of metal-containing proteins\" \/>\n<meta property=\"og:description\" content=\"Raised in a computer-savvy family well-versed in software and information technology, Rohan Jonnalagadda had a strong desire to \u201cdecode\u201d the world around him. 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