Donghan Lee, Ph.D.

Education:Donghan Lee, Ph.D.

B.S., Biochemistry, Yonsei University, 1997
M.S., Physical Biochemistry, Yonsei University, 1999
Ph.D., Biophysics, Swiss Federal Institute of Technology (ETH), 2003

Curriculum Vitae

Current Positions:

James Graham Brown Endowed Chair of Structural Biology
Associate Professor of Medicine, University of Louisville
Director, James Graham Brown Cancer Center NMR Facility

Contact Information:

James Graham Brown Cancer Center
University of Louisville
505 S. Hancock St
Louisville, KY 40202
Phone: 502-852-3591
Fax: 502-852-7979

Website Links:

www.bionmr.org

Research Description:

Molecular functionality is achieved through the three dimensional structure and thus our research focus is to understand the relationship between the structure and the function of biomolecules. Over the last few decades, the knowledge about the relationship between structure and function was greatly expanded via significant improvement in both experimental and computational approaches as well as the large number of available atomic structures. Despite these tremendous advances, the focus of structural biology is based mainly on studying the average conformational states of biomolecules, which serves as a starting point to understand their functionality. However, it becomes increasingly clear that this narrow approach is insufficient and that a description of molecular structure must take into account conformational dynamics that can occur over a broad range of timescale. To address the relationship between conformational dynamics and functionality, my group is utilizing nuclear magnetic resonance (NMR) spectroscopy, which is a powerful technique capable of covering a timescale of motions that covers picoseconds to real-time. Across this entire regime, NMR observables can report on the amplitude of atomic motion, and the kinetics of atomic motion can be ascertained with a wide variety of experimental techniques from real-time to milliseconds and several nanoseconds to picoseconds. Still a four orders of magnitude time (“hidden-time”) window between several nanoseconds and tens of microseconds has remained elusive. For the atomic-level descriptions of the sparsely populated and transient conformations sampled by the motions occurring within “hidden-time” window, we have developed various methods. By utilizing the developed methods as a cornerstone, we are further developing methods to identify the functional conformation for the drug molecule binding, which could be inaccessible with conventional methods.

Representative Publications:

Functional Dynamics

Ban D, Gossert AD, Giller K, Becker S, Griesinger C, Lee D.  Exceeding the limit of dynamics studies on biomolecules using high spin-lock field strengths with a cryogenically cooled probehead.  Journal of Magnetic Resonance 2012 Aug;221:1-4. PMID: 22743535.

Smith CA, Ban D, Pratihar S, Giller K, Schwiegk C, de Groot BL, Becker S, Griesinger C, Lee D.  Population shuffling of protein conformations.  Angewandte Chemie International Edition in English 2015 Jan 2;54(1):207-10. PMID: 25377083.

Smith CA, Ban D, Pratihar S, Giller K, Paulat M, Becker S, Griesinger C, Lee D, de Groot BL.  Allosteric switch regulates protein-protein binding through collective motion.  Proceedings of the National Academy of Sciences USA 2016;113:3269-74. PMID: 26961002. PMCID: PMC4812760.

Pratihar S, Sabo TM, Ban D, Fenwick RB, Becker S, Salvatella X, Griesinger C, Lee D.  Kinetics of the antibody recognition site in the third IgG-binding domain of protein G.  Angewandte Chemie International Edition in English 2016;55:9567-70. PMID: 27345359.
  

Molecular Recognition Mechanism

Fenwick RB, Esteban-Martin S, Richter B, Lee D, Walter KF, Milovanovic D, Becker S, Lakomek NA, Griesinger C, Salvatella X.  Weak long-range correlated motions in a surface patch of ubiquitin involved in molecular recognition.  Journal of the American Chemical Society 2011 Jul 13;133(27):10336-9. PMID: 21634390. PMCID: PMC3686050. 

Ban D, Funk M, Gulich R, Egger D, Sabo TM, Walter KF, Fenwick RB, Giller K, Pichierri F, de Groot BL, Lange OF, Grubmuller H, Salvatella X, Wolf M, Loidl A, Kree R, Becker S, Lakomek NA, Lee D, Lunkenheimer P, Griesinger C.  Kinetics of conformational sampling in ubiquitin.  Angewandte Chemie International Edition in English 2011 Nov 25;50(48):11437-40. PMID: 22113802. 

Ban D, Sabo TM, Griesinger C, Lee D.  Measuring dynamics and kinetic information in the previously inaccessible supra-tc window of nanoseconds to microseconds by solution NMR spectroscopy.  Molecules 2013 Sep 26;18(10):11904-37. PMID: 24077173. [ https://www.mdpi.com/1420-3049/18/10/11904

Michielssens S, Peters JH, Ban D, Pratihar S, Seeliger D, Sharma M, Giller K, Sabo TM, Becker S, Lee D, Griesinger C, de Groot BL.  A designed conformational shift to control protein binding specificity.  Angewandte Chemie International Edition in English 2014 Sep 22;53(39):10367-71. PMID: 25115701. PMCID: PMC4497613.

Developing Methods for the Interconnection Between Function and Structural Motions

Mazur A, Hammesfahr B, Griesinger C, Lee D, Kollar M.  ShereKhan – calculating exchange parameters in relaxation dispersion data from CPMG experiments. nBioinformatics 2013 Jul 15;29(14):1819-20. PMID: 23698862. 

Sabo TM, Trent JO, Lee D.  Population shuffling between ground and high energy excited states.  Protein Science 2015 Nov;24(11):1714-9. PMID: 26316263. PMCID: PMC4622205.  

Carneiro MG, Reddy JG, Griesinger C, Lee D.  Speeding-up exchange-mediated saturation transfer experiments by Fourier transform.  Journal of Biomolecular NMR 2015 Nov;63(3):237-44. PMID: 26350257.  

Chakrabarti KS, Ban D, Pratihar S, Reddy JG, Becker S, Griesinger C, Lee D.  High-power 1H composite pulse decoupling provides artifact free exchange-mediated saturation transfer (EST) experiments.  Journal of Magnetic Resonance 2016 Aug;269:65-69. PMID: 27240144.  

Developing Methods for Specific Purposes to Address Functionalities of Specific Biomolecules

Bromek K, Lee D, Hauhart R, Krych-Goldberg M, Atkinson JP, Barlow PN, Pervushin K.  Polychromatic selective population inversion for TROSY experiments with large proteins.  Journal of the American Chemical Society 2005 Jan 12;127(1):405-11. PMID: 15631491. 

Lee D, Pervushin K, Bischof D, Braun M, Thony-Meyer L.  Unusual heme-histidine bond in the active site of a chaperone.  Journal of the American Chemical Society 2005 Mar 23;127(11):3716-7. PMID: 15771504.  

Lee D, Vogeli B, Pervushin K.  Detection of C’,Ca correlations in proteins using a new time- and sensitivity-optimal experiment.  Journal of Biomolecular NMR 2005 Apr;31(4):273-8. PMID: 15928994. 

Himmel S, Wolff S, Becker S, Lee D, Griesinger C.  Detection and identification of protein-phosphorylation sites in histidine through HNP correlation patterns.  Angewandte Chemie International Edition in English 2010 Nov 15;49(47):8971-4. PMID: 20939030.

Developing Methods for the Investigation of Membrane Proteins

Lee D, Oh ES, Woods Am Couchman JR, Lee W. Solution structure of a syndecan-4 cytoplasmic domain and its interaction with phosphatidylinosition 4, 5-bisphosphate.  Journal of Biological Chemistry 1998 May 22;273(21):13022-9. PMID: 9582338. [http://www.jbc.org/content/273/21/13022.long

Lee D, Hilty C, Wider G, Wuthrich K.  Effective rotational correlation times of proteins from NMR relaxation interference.  Journal of Magnetic Resonance 2006 Jan;178(1):72-6. PMID: 16188473. 

Lee D, Walter KF, Bruckner AK, Hilty C, Becker S, Griesinger C.  Bilayer in small bicelles revealed by lipid-protein interactions using NMR spectroscopy.  Journal of the American Chemical Society 2008 Oct 22;130(42):13822-3. PMID: 28617394. 

Bibow S, Carneiro MG, Sabo TM, Schwiegk C, Becker S, Riek R, Lee D.  Measuring membrane protein bond orientations in nanodiscs via residual dipolar couplings.  Protein Science 2014 Jul;23(7):851-6. PMID: 24752984. PMCID: PMC4088969.

Providing Structural Insights Toward Functionality of Biomolecules

Lee D, Walsh JD, Mikhailenko I, Yu P, Migliorini M, Wu Y, Krueger S, Curtis JE, Harris B, Lockett S, Blacklow SC, Strickland DK, Wang YX.  RAP uses a histidine switch to regulate its interaction with LRP in the ER and Golgi.  Molecular Cell 2006 May 5;22(3):423-30. PMID: 16678114. [ https://www.sciencedirect.com/science/article/pii/S1097276506002590?via%3Dihub

Lee D, Walsh JD, Yu P, Markus MA, Choli-Papadopoulou T, Schwieters CD, Krueger S, Draper DE, Wang YX.  The structure of free L11 and functional dynamics of L11 in free, L11-rRNA(58 nt) binary and L11-rRNA(58 nt)-thiostrepton ternary complexes.  Journal of Molecular Biology 2007 Apr 6;367(4):1007-22. PMID: 17292917. PMCID: PMC2045704. 

Rodriguez-Castaneda F, Maestre-Martinez M, Coudevylle N, Dimova K, Junge H, Lipstein N, Lee D, Becker S, Brose N, Jahn O, Carlomagno T, Griesinger C.  Modular architecture of Munc13/calmodulin complexes: dual regulation by Ca2+ and possible function in short-term synaptic plasticity.  EMBO Journal 2010 Feb 3;29(4):680-91. PMID: 20010694. PMCID: PMC2830703. 

Carneiro MG, Koharudin LM, Ban D, Sabo TM, Trigo-Mourino P, Mazur A, Griesinger C, Gronenborn AM, Lee D.  Sampling of glycan-bound conformers by the anti-HIV lectin Oscillatoria agardii agglutinin in the absence of sugar.  Angewandte Chemie International Edition in English 2015 May 26;54(22):6462-5. PMID: 25873445. PMCID: PMC4480366.

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