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<p>The Berndsen lab is interested in two areas: the enzymatic mechanisms of acyl transfer and viral tethering by the protein Tetherin. Lab projects on these topics use a variety of techniques and approaches from measurement of enzyme activity to observing protein structure through X-ray crystallography and computational methods.</p>
<p>We also work with collaborators on and off campus to help answer questions involving protein structure and function.</p>
<p>There are several opportunities for undergraduate students to perform research in the lab both during the academic year and summer, please contact Dr. Berndsen for more information.</p>
<p>A complete <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=berndsen+ce">list</a> of publications from the lab or on <a href="https://scholar.google.com/citations?user=H5dU9y4AAAAJ&hl=en">Google Scholar</a>.</p>
<p>We also post data for certain projects on <a href="https://osf.io/zb3xk/">OSF</a>.</p>
<p>The Berndsen lab is also associated with the <a href="http://www.jmu.edu/genomics/">JMU Center for Genome and Metagenome Studies</a>.</p>
<hr />
<div class="figure">
<img src="images/vip.png" alt="Model and SAXS fit of Legionella VipF from Young, et al., 2016" style="width:50.0%" />
<p class="caption">Model and SAXS fit of <em>Legionella</em> VipF from Young, <em>et al.</em>, 2016</p>
</div>
<div id="enzymatic-mechanism-of-acyl-transfer" class="section level2">
<h2>Enzymatic Mechanism of Acyl Transfer</h2>
<p>Cellular proteins are often modified with chemical moieties such as phosphate or methyl groups in order to alter the function of these proteins in response to changes in the environment or during the cell cycle. Two of these post-translational modifications, acetylation and ubiquitination, involve a reaction of a thioester with an amine. While the reaction chemistry is straightforward, the enzymatic mechanism of transfer is not clear and there are a variety of protein structures that can do this chemistry. We aim to determine the catalytic mechanism of these enzymes via biochemical and structural methods to understand:</p>
<ul>
<li><p>how substrates bind</p></li>
<li><p>the enzyme increases the rate of the reaction</p></li>
<li><p>the role of changes in the enzyme structure in the reaction chemistry</p></li>
<li><p>how substrate specificity is encoded by the enzyme</p></li>
</ul>
<p>Current projects are focused on ubiquitin/ubiquitin-like activating enzymes, cleavage of ubiquitin precursors, and enzymatic modification of protein lysines.</p>
<div id="previous-work-by-the-lab-on-this-project" class="section level4">
<h4>Previous work by the lab on this project:</h4>
<p>(undergraduate authors are indicated in <strong>bold</strong>)</p>
<p>Padala P, Oweis W, Mashahreh B, Soudah N, Cohen-Kfir E, <strong>Todd EA</strong>, Berndsen CE, Wiener R. Novel insights into the interaction of UBA5 with UFM1 via a UFM1-interacting sequence. Sci Rep. 2017 Mar 30;7(1):508. doi: 10.1038/s41598-017-00610-0. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428781/">PMID: 28360427</a></p>
<p><strong>Young BH</strong>, <strong>Caldwell TA</strong>, <strong>McKenzie AM</strong>, Kokhan O, Berndsen CE. (2016) Characterization of the structure and catalytic activity of Legionella pneumophila VipF. Proteins. Oct;84(10):1422-30. <a href="http://onlinelibrary.wiley.com/doi/10.1002/prot.25087/abstract">doi: 10.1002/prot.25087.</a> PMID: 27315603</p>
<p>Oweis W, Padala P, Hassouna F, Cohen-Kfir E, <strong>Gibbs DR</strong>, <strong>Todd EA</strong>, Berndsen CE, Wiener R. (2016) Trans-Binding Mechanism of Ubiquitin-like Protein Activation Revealed by a UBA5-UFM1 Complex. Cell Rep. Sep 20;16(12):3113-20. <a href="https://www.sciencedirect.com/science/article/pii/S2211124716311482?via%3Dihub">doi: 10.1016/j.celrep.2016.08.067.</a> PMID: 27653677</p>
<hr />
<div class="figure">
<img src="images/bam2amylosetop.png" alt="Model of \beta amylase 2 bound to substrates" style="width:50.0%" />
<p class="caption">Model of <span class="math inline">\(\beta\)</span> amylase 2 bound to substrates</p>
</div>
</div>
</div>
<div id="structure-and-function-of-beta-amylase-enzymes" class="section level2">
<h2>Structure and function of <span class="math inline">\(\beta\)</span> amylase enzymes</h2>
<p>In plants, <span class="math inline">\(\beta\)</span> amylases cleave <span class="math inline">\(\alpha\)</span> 1-4 linkages between dextrose residues in starch. This enzymatic activity produces maltose which can then fuel other processes in the plant. In <em>Arabidopsis thaliana</em> there are 9 <span class="math inline">\(\beta\)</span> amylases however little is known about the structure and biochemistry of these enzyme. In collaboration with <a href="https://www.jmu.edu/biology/people/current-people/faculty/faculty-monroe.shtml">Dr. Jon Monroe in the JMU Biology Department</a> we are working to characterize the structure and function of these crucial enzymes for plant metabolism</p>
<div id="previous-work-by-the-lab-on-this-project-1" class="section level4">
<h4>Previous work by the lab on this project:</h4>
<p>(undergraduate authors are indicated in <strong>bold</strong>)</p>
<p>Monroe JD, <strong>Pope LE</strong>, <strong>Breault JS</strong>, Berndsen CE, Storm AR. Quaternary Structure, Salt Sensitivity, and Allosteric Regulation of <span class="math inline">\(\beta\)</span>-AMYLASE2 From <em>Arabidopsis thaliana</em></p>
<p>Storm AR, <strong>Kohler MR</strong>, Berndsen CE, Monroe JD. Glutathionylation Inhibits the Catalytic Activity of <em>Arabidopsis</em> <span class="math inline">\(\beta\)</span>-Amylase3 but Not That of Paralog <span class="math inline">\(\beta\)</span>-Amylase1. Biochemistry. 2018 Feb 6;57(5):711-721. doi: 10.1021/acs.biochem.7b01274.</p>
<p>Monroe JD, <strong>Breault JS</strong>, <strong>Pope LE</strong>, <strong>Torres CE</strong>, <strong>Gebrejesus TB</strong>, Berndsen CE, Storm AR. <em>Arabidopsis</em> <span class="math inline">\(\beta\)</span>-amylase2 is a K+-requiring, catalytic tetramer with sigmoidal kinetics. Plant Physiol. 2017 Oct 24. pii: pp.01506.2017. doi: 10.1104/pp.17.01506.</p>
<hr />
<div class="figure">
<img src="images/Transitionshuman.png" alt="Simulated pulling of human Tetherin from Ozcan and Berndsen, 2017" style="width:50.0%" />
<p class="caption">Simulated pulling of human Tetherin from Ozcan and Berndsen, 2017</p>
</div>
</div>
</div>
<div id="viral-tethering-by-human-tetherin" class="section level2">
<h2>Viral Tethering by human Tetherin</h2>
<p>All humans contain a simple protein known as BST-2 or Tetherin which has the innate ability to latch onto budding viruses and tether the virus to the host cell membrane. Other than a mechanical tether, there are no known functions for Tetherin and it is not exactly clear how this protein functions. We combine biophysical and computational approaches to determine the structural mechanism of viral tethering and how viral antagonists block the function of Tetherin</p>
<div id="previous-work-by-the-lab-on-this-project-2" class="section level4">
<h4>Previous work by the lab on this project:</h4>
<p>(undergraduate authors are indicated in <strong>bold</strong>)</p>
<p><strong>Ozcan KA</strong>, Berndsen CE Bending of the BST-2 coiled-coil during viral budding. (2017) Proteins. 2017 Aug 4. <a href="http://onlinelibrary.wiley.com/doi/10.1002/prot.25362/abstract;jsessionid=2584DD9CB5C8BCDCDCB6CF95A2DE368F.f02t04">doi: 10.1002/prot.25362.</a> or <a href="https://www.biorxiv.org/content/early/2017/07/11/160242">BioRxiv</a></p>
<p><strong>Du Pont KE</strong>, <strong>McKenzie AM</strong>, Kokhan O, Sumner I, Berndsen CE. (2016) The Disulfide Bonds within BST-2 Enhance Tensile Strength during Viral Tethering. Biochemistry. Feb 16;55(6):940-7. <a href="https://pubs.acs.org/doi/10.1021/acs.biochem.5b01362">doi: 10.1021/acs.biochem.5b01362.</a></p>
<p>Welbourn S, Kao S, <strong>Du Pont KE</strong>, Andrew AJ, Berndsen CE, Strebel K. (2015) Positioning of cysteine residues within the N-terminal portion of the BST-2/tetherin ectodomain is important for functional dimerization of BST-2. J Biol Chem. Feb 6;290(6):3740-51. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319038/">doi: 10.1074/jbc.M114.617639. PMID: 25525265</a></p>
<hr />
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<div id="support-and-funding" class="section level2">
<h2>Support and Funding</h2>
<p>The work of the Berndsen lab is graciously supported by:</p>
<ul>
<li><p>National Science Foundation</p></li>
<li><p>Jeffress Memorial Trust for Interdisciplinary Research</p></li>
<li><p>4-VA organization</p></li>
<li><p>Hamilton Syringe Company</p></li>
<li><p>U.S.-Israel Binational Science Foundation</p></li>
</ul>
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