{"id":4799,"date":"2018-01-05T18:50:00","date_gmt":"2018-01-05T23:50:00","guid":{"rendered":"https:\/\/www.med.unc.edu\/biochem\/directory\/andrew-l-lee\/"},"modified":"2025-09-03T15:58:01","modified_gmt":"2025-09-03T19:58:01","slug":"andrew-l-lee","status":"publish","type":"directory","link":"https:\/\/www.med.unc.edu\/biochem\/directory\/andrew-l-lee\/","title":{"rendered":"Andrew L. &#8220;Drew&#8221; Lee"},"content":{"rendered":"<p style=\"text-align: center\"><em><strong><span class=\"blue\">Professor of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy<\/span><\/strong><\/em><\/p>\n<p style=\"text-align: center\">Joint Appointment in Biochemistry and Biophysics<\/p>\n<p style=\"text-align: center\"><span class=\"discreet\" style=\"color: #333333\">(PhD &#8211; PhD &#8211; UC Berkeley)<\/span><\/p>\n<p style=\"text-align: center\"><strong>Trained Mentor<\/strong><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-10603 aligncenter\" src=\"https:\/\/www.med.unc.edu\/biochem\/wp-content\/uploads\/sites\/795\/2019\/08\/Faculty-OGE-Trained-mentor-badge-400dpi-for-website-300x181.png\" alt=\"Trained Faculty Mentor endorsed by Office of Graduate Ed UNC Chapel Hill\" width=\"300\" height=\"181\" srcset=\"https:\/\/www.med.unc.edu\/biochem\/wp-content\/uploads\/sites\/795\/2019\/08\/Faculty-OGE-Trained-mentor-badge-400dpi-for-website-300x181.png 300w, https:\/\/www.med.unc.edu\/biochem\/wp-content\/uploads\/sites\/795\/2019\/08\/Faculty-OGE-Trained-mentor-badge-400dpi-for-website-768x464.png 768w, https:\/\/www.med.unc.edu\/biochem\/wp-content\/uploads\/sites\/795\/2019\/08\/Faculty-OGE-Trained-mentor-badge-400dpi-for-website-1024x619.png 1024w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><\/p>\n<div>\n<h3><span class=\"blue\">RESEARCH<\/span><\/h3>\n<p><strong>Protein dynamics and NMR spectroscopy<\/strong><\/p>\n<p>Nearly all biological processes are driven by the same fundamental event: protein conformational changes.\u00a0The dynamic nature of proteins is now widely appreciated but not well understood since dynamics are not evident from static structural images. Our research is aimed at atomic resolution characterizations of protein dynamics and how dynamics contribute to function, especially allosteric communication and regulation. Towards this goal, we employ protein NMR spectroscopy in conjunction with other chemical biology and biophysical tools. NMR is ideal for our studies, as hundreds \u2013 even thousands \u2013 of structural and motional \u201cspin probes\u201d are uniformly distributed throughout any given protein.<\/p>\n<h3><span class=\"blue\">Research Projects<\/span><\/h3>\n<p><strong>Homodimers for study of protein allostery, I \u2013 Chorismate Mutase<\/strong><\/p>\n<p>From our work on thymidylate synthase (below), we have learned that homodimers offer a powerful and attractive approach to study how allostery works in proteins. Despite many decades of biochemical and structural work on allosteric systems (enzymes, receptors, etc.) and the fact that allostery underlies biological regulation, the basic details of how allostery works are not understood. We have worked out an approach for NMR study of symmetric homodimers that has great promise for observing the dynamic processes underlying allosteric function. Part of the approach puts click chemistry to use to create covalently linked \u201cmixed labeled dimers\u201d (MLDs), which provide clear signals to track allosteric movements. The enzyme chorismate mutase (CM, in the aromatic amino acid biosynthesis pathway) is an ideal system for developing this approach since it possesses all the hallmarks of classical allostery, including tense (\u201cT\u201d) and relaxed (\u201cR\u201d) allosteric conformations. NMR observation of individual residues can be correlated with allosteric function detected in enzymatic assays. Measuring specific relaxation rates of chemical groups \u2013 such as with methyl-TROSY for larger proteins \u2013 captures the dynamics of these different groups to provide molecular insight.<\/p>\n<p><strong>Homodimers for study of protein allostery, II \u2013 Thymidylate Synthase<\/strong><\/p>\n<p>The other homodimeric enzyme of interest in the lab is thymidylate synthase (TS). Like CM, it is also symmetric and allosteric (and about the same size, ~60 kDa), but whereas CM displays positive cooperativity between its two active sites, TS activity is negatively cooperative (specifically, \u201chalf-the-sites-reactive\u201d). Further, its dimer interface is a beta-sheet structure whereas CM is all alpha-helical; thus the two systems provide an interesting contrast. It was on TS that we initially developed the mixed-labeled-dimer (MLD) approach now being pursued on both systems. Most recently we showed using NMR that rapid motions on the picosecond-nanosecond timescale provide an entropically driven mechanism for cooperative binding of substrate (for human TS), and that, non-intuitively, these functional motions in hTS are entirely dependent on a completely disordered N-terminal tail of ~25 amino acids. How this can occur will be the subject of further work.<\/p>\n<p><strong>Other past and present projects<\/strong><\/p>\n<p>Past work on the lab focused on the dynamic and allosteric properties of smaller protein domains (e.g. PDZ domains) and regulatory proteins or enzymes (CheY, DHFR). One of our current interests is in understanding the dynamic properties and conformational changes taking place in engineered allosteric proteins that respond to light \u2013 \u2018optogenetic\u2019 proteins.<\/p>\n<p><strong>NMR and other methods<\/strong><\/p>\n<p>How do we characterize protein dynamics?\u00a0 Our preferred method is heteronuclear NMR spectroscopy, which is uniquely suited to study both structure <em>and<\/em> dynamics in proteins and other biological macromolecules. A major advantage of NMR is that spectroscopic probes are <em>distributed uniformly throughout the biomolecule<\/em>, such as NH or CH atom pairs, providing large amounts of molecular information.\u00a0To gain information on protein dynamics, NMR spin relaxation is highly sensitive to molecular motion over a range of timescales. We look at the relaxation properties of <sup>15<\/sup>N, <sup>13<\/sup>C, <sup>1<\/sup>H, and <sup>2<\/sup>H spins located throughout the protein scaffold, and interpret these in terms of amplitudes and timescales of individual bond vectors. Slower motions on the microsecond-millisecond timescale can be detected to yield site-specific kinetic, thermodynamic, and structural information on the switching between discrete conformational states. In many cases, these NMR-relaxation dynamics are used to complement other structural data from X-ray crystallography, or thermodynamic and kinetic biophysical measurements using methods such as fluorescence spectroscopy, calorimetry, amide hydrogen exchange, and molecular dynamics simulations. With the larger systems now under study (CM, TS), methyl-TROSY based experiments have become indispensable.<\/p>\n<h3><span class=\"blue\">PUBLICATIONS<\/span><\/h3>\n<p><a class=\"external-link\" title=\"Andrew L Lee publications UNC\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/myncbi\/browse\/collection\/40134635\/?sort=date&amp;direction=ascending\" target=\"_self\" rel=\"noopener noreferrer\"><span class=\"normalSizeFont\" style=\"color: #3187b6;line-height: 1.3em\"><span class=\"discreet\">click<\/span><\/span><span class=\"discreet\"> for Full Publication List for Dr. Andrew Lee<\/span><\/a><\/p>\n<hr \/>\n<h3><span class=\"blue\"><span style=\"color: #3187b6\">Lab Contact:<\/span><\/span><\/h3>\n<p>Lab Rooms: 4109 Marsico Hall<\/p>\n<p>Lab Phone: 919-966-7821<\/p>\n<p><span class=\"discreet\">\u00a0<\/span><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p><!-- description --> <\/p>\n<p class='lead'>Research: Protein dynamics, allostery, NMR spectroscopy, click chemistry, protein biophysics, thymidylate synthase<\/p>\n","protected":false},"featured_media":30284,"template":"","meta":{"_acf_changed":false,"layout":"","cellInformation":"","apiCallInformation":"","_links_to":"","_links_to_target":""},"class_list":["post-4799","directory","type-directory","status-publish","has-post-thumbnail","hentry","odd"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Andrew L. &quot;Drew&quot; 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Lee"}]},{"@type":"WebSite","@id":"https:\/\/www.med.unc.edu\/biochem\/#website","url":"https:\/\/www.med.unc.edu\/biochem\/","name":"UNC Biochemistry and Biophysics","description":"","publisher":{"@id":"https:\/\/www.med.unc.edu\/biochem\/#organization"},"potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/www.med.unc.edu\/biochem\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-US"},{"@type":"Organization","@id":"https:\/\/www.med.unc.edu\/biochem\/#organization","name":"UNC Department of Biochemistry and Biophysics","url":"https:\/\/www.med.unc.edu\/biochem\/","logo":{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/www.med.unc.edu\/biochem\/#\/schema\/logo\/image\/","url":"https:\/\/www.med.unc.edu\/biochem\/wp-content\/uploads\/sites\/795\/2017\/06\/BiochemistryAndBiophysics_logo_2c_rgb_v.png","contentUrl":"https:\/\/www.med.unc.edu\/biochem\/wp-content\/uploads\/sites\/795\/2017\/06\/BiochemistryAndBiophysics_logo_2c_rgb_v.png","width":488,"height":400,"caption":"UNC Department of Biochemistry and Biophysics"},"image":{"@id":"https:\/\/www.med.unc.edu\/biochem\/#\/schema\/logo\/image\/"},"sameAs":["https:\/\/www.facebook.com\/uncbiochemistryandbiophysics\/","https:\/\/x.com\/UNC_BCBP","https:\/\/www.instagram.com\/unc_bcbp\/","https:\/\/www.linkedin.com\/in\/unc-dept-of-biochem-biophysics-17a6187b\/"]}]}},"_upd_display_name":["Andrew L. \"Drew\" Lee"],"_upd_reverse_display_name":["Lee, Andrew L. \"Drew\""],"_upd_last_name":["Lee"],"_upd_first_name":["Andrew L. \"Drew\""],"_upd_sortorder_override":[],"_upd_sortorder":["1"],"_upd_gallery_summary":["<p class=\" \"><span style=\"color: #333333\"><em><strong><span class=\"blue\"><i>Professor of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy<\/i><\/span><\/strong><\/em><\/span><\/p>\r\nTRAINED MENTOR\r\n\r\nResearch: Protein dynamics, allostery, NMR spectroscopy, click chemistry, protein biophysics, thymidylate synthase\r\n<span style=\"color: #333333\"><span style=\"color: #333333\"><span style=\"color: #333333;line-height: 1.43em\">CB# 7295, Lineberger Cancer Ctr\r\n<\/span><\/span><\/span><span style=\"color: #333333\"><span style=\"color: #333333\"><span style=\"line-height: 1.43em;color: #333333\">tel: 919-966-2151 I<\/span> <a class=\"email-link\" style=\"line-height: 1.43em\" title=\"\" href=\"mailto:jdg@med.unc.edu\" target=\"_self\">Email<\/a>\r\n<a href=\"https:\/\/tarheels.live\/leelab\/\">Lee lab website<\/a><\/span><\/span>"],"_upd_no_link":[],"_upd_degree1":[],"_upd_degree2":[],"_upd_email":[[{"email_text":"drewlee@unc.edu"}]],"_upd_phone":[[{"phone_text":"919-966-7821","phone_type":"Office Phone"}]],"_upd_address":[[{"address":{"address-1":"Lee Lab","address-2":"4109 Marsico Hall","campus-box":"","city":"Chapel Hill","state":"NC","zip":"27599-7295"}}]],"_links":{"self":[{"href":"https:\/\/www.med.unc.edu\/biochem\/wp-json\/wp\/v2\/directory\/4799","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.med.unc.edu\/biochem\/wp-json\/wp\/v2\/directory"}],"about":[{"href":"https:\/\/www.med.unc.edu\/biochem\/wp-json\/wp\/v2\/types\/directory"}],"version-history":[{"count":3,"href":"https:\/\/www.med.unc.edu\/biochem\/wp-json\/wp\/v2\/directory\/4799\/revisions"}],"predecessor-version":[{"id":31799,"href":"https:\/\/www.med.unc.edu\/biochem\/wp-json\/wp\/v2\/directory\/4799\/revisions\/31799"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.unc.edu\/biochem\/wp-json\/wp\/v2\/media\/30284"}],"wp:attachment":[{"href":"https:\/\/www.med.unc.edu\/biochem\/wp-json\/wp\/v2\/media?parent=4799"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}