Research Area


Site-specific Protein Modification

  • "Marking-Activation-Coupling" approach to attach various functional groups to the protein

  • Site-specific, authentic protein modification

Genetic Incorporation of
Non-canonical Amino Acids into Proteins

  • Development of new methods for the incorporation of ncAAs into proteins

  • Design and engineering of translational machineries for the genetic code expansion

Phosphoserine Incorporation

  • Structural biology of phosphoproteins

  • Detailed mapping of protein kinase signaling networks

  • Anti-cancer drug design based on activated target-ligand structures

  • High-throughput screening of kinase inhibitors

Protein Engineering and Directed Evolution

  • Rational design of enzymes based on structural analysis

  • Molecular evolution of proteins for the enhanced properties

Hee-Sung Park
박희성


  • 2022~ Professor
    Dept. of Chemistry, KAIST

  • 2013-2022 Associate Professor
    Dept. of Chemistry, KAIST

  • 2009-2013 Assistant Professor
    Dept. of Chemistry, KAIST

  • 2008-2009 Research Faculty
    Dept. of Molecular Biophysics & Biochemistry,
    Yale University

  • 2005-2008 Postdoctoral Associate
    under Prof. Dieter Söll
    at Dept. of Molecular Biophysics & Biochemistry,
    Yale University

  • 2000-2005 Postdoctoral Associate
    under Prof. Hak-Sung Kim
    at Dept. of Biological Sciences, KAIST

  • 2000 Ph.D. in Chemical Engineering, KAIST

  • 1996 M.S. in Biological Sciences, KAIST

  • 1994 B.S. in Food Science and Biotechnology,
    Seoul National University

Current Members

Joo-Chan Kim김주찬Ph.D. candidate

현재 랩장을 맡고 있습니다.
interests:
site-specific protein modification
bioorthogonal chemistry
computational chemistry

YouJin Kim김유진Ph.D. candidate

interests:
cryo-EM,
in situ cryo-ET,
structure-based study of PTMs

SuHo Cho조수호Ph.D. candidate

interests:
protein modification
ubiquitin
protein chiral activation


Alumni

Selected Publications

Site-specific Protein Modification

Science, 354(6312):623-626. (2016)


All Publications

† : these authors have contributed to the work equally.
* : corresponding author

2024

  1. YouJin Kim, Suho Cho, Joo-Chan Kim, and Hee-Sung Park*
    tRNA Engineering Strategies for Genetic Code Expansion
    Frontiers in Genetics, Mar 2024; 15:1373250.
    DOI: 10.3389/fgene.2024.1373250

2023

  1. Marcel Janis Beha, Joo-Chan Kim, San Hae Im, Yunsu Kim, Seungju Yang, Juhee Lee, Yu Ri Nam, Haeshin Lee, Hee-Sung Park*, and Hyun Jung Chung*
    Bioorthogonal CRISPR/Cas9-Drug Conjugate: A Combinatorial Nanomedicine Platform
    Advanced Science, Sep 2023; 10(27):2302253.
    DOI: 10.1002/advs.202302253

  2. Neha Jain, Prasad M. Sonawane, Haoyan Liu, Arkaprava Roychaudhury, Youngseob Lee, Jongkeol An, Donghyeon Kim, Dongwook Kim, Yunsu Kim, Yeu-Chun Kim, Kyung-Bin Cho, Hee-Sung Park, Cheol-Hee Kim*, and David G. Churchill*
    "Lighting Up" Fluoride: Cellular Imaging and Zebrafish Model Interrogations using a Simple ESIPT-based Mycophenolic Acid Precursor-based Probe
    Analyst, May 2023; 148:2609-2615.
    DOI: 10.1039/D3AN00646H

  3. Deokhee Kang, Do-Wook Kim, Joo-Chan Kim, and Hee-Sung Park*
    A Versatile Strategy for Screening Custom-Designed Warhead-Armed Cyclic Peptide Inhibitors
    Angewandte Chemie International Edition, Feb 2023; 62(7):e202214815.
    DOI: 10.1002/anie.202214815

2022

  1. Seonghoon Kim, Hee-Sung Park, and Byung-Ha Oh*
    Computational Design of an Apoptogenic Protein that Binds BCL-xL and MCL-1 Simultaneously and Potently
    Computational and Structural Biotechnology Journal, Jun 2022; 20:3019-3029.
    DOI: 10.1016/j.csbj.2022.06.021

  2. Prasad M. Sonawane, Woohyun Lee, Yunsu Kim, Arkaprava Roychaudhury, Vikas K. Bhosale, Donghyeon Kim, Hee-Sung Park, Cheol-Hee Kim*, and David G. Churchill*
    Phosphinate-benzoindocyanin Fluorescent Probe for Endogenous Mitochondrial Peroxynitrite Detection in Living Cells and Gallbladder Access in Inflammatory Zebrafish Animal Models
    Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Feb 2022; 267(2):120568.
    DOI: 10.1016/j.saa.2021.120568

2021

  1. Prasad M. Sonawane, Tesla Yudhistira, Mahesh B. Halle, Arkaprava Roychaudhury, Yunsu Kim, Sachin S. Surwase, Vikas K. Bhosale, Juhyeon Kim, Hee-Sung Park, Yeu-chun Kim, Cheol-Hee Kim*, and David G. Churchill*
    A Water-soluble Boronate masked Benzoindocyanin Fluorescent Probe for the Detection of Endogenous Mitochondrial Peroxynitrite in Live Cells and Zebrafish as Inflammation Models
    Dyes and Pigments, Jul 2021; 191:109371.
    DOI: 10.1016/j.dyepig.2021.109371

  2. Donghyeok Gang and Hee-Sung Park*
    Noncanonical Amino Acids in Synthetic Biosafety and Post-translational Modification Studies
    ChemBioChem, Feb 2021; 22(3):460-468.
    DOI: 10.1002/cbic.202000437

2020

  1. Phuong Thi Mai Duong, Anh Thi Ngoc Bui, Seong-Ok Kim, Hee-Sung Park*, Yeon-Soo Seo, and Byong-Seok Choi*
    The Interaction between Ubiquitin and Yeast Polymerase η C-terminus Does Not Require the UBZ Domain
    FEBS Letters, Jun 2020; 594(11):1726-1737.
    DOI: 10.1002/1873-3468.13783

2019

  1. Ina Yoon, Miso Nam, Hoi Kyoung Kim, Hee-Sun Moon, Sungmin Kim, Jayun Jang, Ji Ae Song, Seung Jae Jeong, Sang Bum Kim, Seongmin Cho, Younha Kim, Jihye Lee, Won Suk Yang, Hee Chan Yoo, Kibum Kim, Min-Sun Kim, Aerin Yang, Kyukwang Cho, Hee-Sung Park, Geum-Sook Hwang, Kwang Yeon Hwang, Jung Min Han, Jong Hyun Kim*, and Sunghoon Kim*
    Glucose-dependent Control of Leucine Metabolism by Leucyl-tRNA Synthetase 1
    Science, Nov 2019; 367(6474):205-210.
    DOI: 10.1126/science.aau2753

  2. Kyung Jin Lee, Deokhee Kang, and Hee-Sung Park*
    Site-Specific Labeling of Proteins Using Unnatural Amino Acids
    Molecules and Cells, May 2019; 42(5):386-396.
    DOI: 10.14348/molcells.2019.0078

2018

  1. Mahesh B. Halle, Kyung Jin Lee, Tesla Yudhistira, Jae Hyuck Choi, Hee-Sung Park, and David G. Churchill*
    A Hemicyanine-Embedded Diphenylselenide-Containing Probe "HemiSe" in which SePh2 Stays Reduced for Selective Detection of Superoxide in Living Cells
    Chemistry - An Asian Journal, Dec 2018; 13(24):3895-3902.
    DOI: 10.1002/asia.201801339

  2. Donghyeok Gang, Do Wook Kim, and Hee-Sung Park*
    Cyclic Peptides: Promising Scaffolds for Biopharmaceuticals
    Genes, Nov 2018; 9(11):557.
    DOI: 10.3390/genes9110557

  3. Mahesh B. Halle, Tesla Yudhistira, Kyung Jin Lee, Jae Hyuck Choi, Youngsam Kim, Hee-Sung Park, and David G. Churchill*
    Overriding Phthalate Decomposition When Exploring Mycophenolic Acid Intermediates as Selenium-Based ROS Biological Probes
    ACS Omega, Oct 2018; 3(10):13474-13483.
    DOI: 10.1021/acsomega.8b01571

  4. Jihye Ahn, Jin Gyeong Lee, Chuevin Chin, Suna In, Aerin Yang, Hee-Sung Park, Jaehoon Kim*, and Jeong Hyeon Park*
    MSK1 Functions as a Transcriptional Coactivator of p53 in the Regulation of p21 Gene Expression
    Experimental and Molecular Medicine, Oct 2018; 50:1-12.
    DOI: 10.1038/s12276-018-0160-8

  5. Hyunhee Kim, Hyelim Jo, Hogyu David Seo, Hee-Sung Park, and Daeyoup Lee*
    Chd1p Recognizes H3K36Ac to Maintain Nucleosome Positioning Near the Transcription Start Site
    Biochemical and Biophysical Research Communications, Sep 2018; 503(3):1200-1206.
    DOI: 10.1016/j.bbrc.2018.07.025

  6. Samira Husen Alamudi, Dongdong Su, Kyung Jin Lee, Jung Yeol Lee, José Luis Belmonte-Vázquez, Hee-Sung Park, Eduardo Peña-Cabrera*, and Young-Tae Chang*
    A Palette of Background-Free Tame Fluorescent Probes for Intracellular Multi-color Labelling in Live Cells
    Chemical Science, Jan 2018; 9:2376-2383.
    DOI: 10.1039/C7SC04716A

2017

  1. Sang-Woo Kim, Kyung Jin Lee, Sinil Kim, Jihyo Kim, Kyukwang Cho, Hyeon-Su Ro*, and Hee-Sung Park*
    Genetic Incorporation of Nε-Acetyllysine Reveals a Novel Acetylation-SUMOylation Switch in Yeast
    Biochimica et Biophysica Acta (BBA) - General Subjects, Nov 2017; 1861(11B):3030-3037.
    DOI: 10.1016/j.bbagen.2017.02.002

  2. Siyeong Yang, Hongki Kim, Kyung Jin Lee, Seul Gee Hwang, Eun-Kyung Lim, Juyeon Jung, Tae Jae Lee, Hee-Sung Park*, Taejoon Kang*, and Bongsoo Kim*
    Attomolar Detection of Extracellular microRNAs Released from Living Prostate Cancer Cells by a Plasmonic Nanowire Interstice Sensor
    Nanoscale, Oct 2017; 9:17387-17395.
    DOI: 10.1039/C7NR04386D

  3. Aerin Yang, Kyukwang Cho, and Hee-Sung Park*
    Chemical Biology Approaches for Studying Posttranslational Modifications
    RNA Biology, Sep 2017; 15(4-5):427-440.
    DOI: 10.1080/15476286.2017.1360468

  4. Sandip V. Mulay, Youngsam Kim, Kyung Jin Lee, Tesla Yudhistira, Hee-Sung Park, and David G. Churchill*
    A Fluorogenic and Red-shifted Diphenyl Phosphinate-based Probe for Selective Peroxynitrite Detection as Demonstrated in Fixed Cells
    New Journal of Chemistry, Sep 2017; 41:11934-11940.
    DOI: 10.1039/C7NJ02530K

  5. Tesla Yudhistira, Sandip V. Mulay, Kyung Jin Lee, Youngsam Kim, Hee-Sung Park, and David G. Churchill*
    Thiomaleimide Functionalization for Selective Biological Fluorescence Detection of Peroxynitrite as Tested in HeLa and RAW 264.7 Cells
    Chemistry - An Asian Journal, Aug 2017; 12(15):1927-1934.
    DOI: 10.1002/asia.201700527

  6. Songmi Han, Aerin Yang, Soonjang Lee, Han-Woong Lee, Chan Bae Park*, and Hee-Sung Park*
    Expanding the Genetic Code of Mus musculus
    Nature Communications, Feb 2017; 8:14568.
    DOI: 10.1038/ncomms14568

2016

  1. Steven Z. Josefowicz*, Miho Shimada, Anja Armache, Charles H. Li, Rand M. Miller, Shu Lin, Aerin Yang, Brian D. Dill, Henrik Molina, Hee-Sung Park, Benjamin A. Garcia, Jack Taunton, Robert G. Roeder*, and C. David Allis*
    Chromatin Kinases Act on Transcription Factors and Histone Tails in Regulation of Inducible Transcription
    Molecular Cell, Oct 2016; 64(2):347-361.
    DOI: 10.1016/j.molcel.2016.09.026

  2. Aerin Yang, Sura Ha, Jihye Ahn, Rira Kim, Sungyoon Kim, Younghoon Lee, Jaehoon Kim, Dieter Söll*, Hee-Yoon Lee*, and Hee-Sung Park*
    A Chemical Biology Route to Site-Specific Authentic Protein Modifications
    Science, Sep 2016; 354(6312):623-626.
    DOI: 10.1126/science.aah4428

  3. Jieon Lee, Il-Soo Park, Ginam Park, Kyukwang Cho, Hee-Sung Park, and Del-Hee Min*
    A Robust and Quantitative Assay Platform for Multiplexed, High Throughput Screening of Protein Kinase Inhibitors
    Chemical Communications, Sep 2016; 52:12112-12115.
    DOI: 10.1039/C6CC05834E

  4. Euihan Jung, Seonghui Jang, Jungmin Lee, Youngmi Kim, Heegwon Shin, Hee-Sung Park, and Younghoon Lee*
    Truncated SRA RNA Derivatives Inhibit Estrogen Receptor-α-mediated Transcription
    Molecular Biology Reports, Jul 2016; 43:1019-1025.
    DOI: 10.1007/s11033-016-4039-2

  5. Samira Husen Alamudi, Rudrakanta Satapathy, Jihyo Kim, Dongdong Su, Haiyan Ren, Rajkumar Das, Lingna Hu, Enrique Alvarado-Martínez, Jung Yeol Lee, Christian Hoppmann, Eduardo Peña-Cabrera, Hyung-Ho Ha, Hee-Sung Park*, Lei Wang* and Young-Tae Chang*
    Development of Background-Free Tame Fluorescent Probes for Intracellular Live Cell Imaging
    Nature Communications, Jun 2016; 7:11964.
    DOI: 10.1038/ncomms11964

2015

  1. Gil Ju Seo, Aerin Yang, Brandon Tan, Sungyoon Kim, Qiming Liang, Younho Choi, Weiming Yuan, Pinghui Feng, Hee-Sung Park, and Jae U. Jung*
    Akt Kinase-Mediated Checkpoint of cGAS DNA Sensing Pathway
    Cell Reports, Oct 2015; 13(2):440-449.
    DOI: 10.1016/j.celrep.2015.09.007

2014

  1. Mude Shi, Hyelim Cho, Kyung-Soo Inn, Aerin Yang, Zhen Zhao, Qiming Liang, Gijs A. Versteeg, Samad Amini-Bavil-Olyaee, Lai-Yee Wong, Berislav V. Zlokovic, Hee-Sung Park, Adolfo García-Sastre, and Jae U. Jung*
    Negative Regulation of NF-κB Activity by Brain-specific TRIpartite Motif protein 9
    Nature Communications, Sep 2014; 5:4820.
    DOI: 10.1038/ncomms5820

  2. Yonghwang Ha, Aerin Yang, Seyoung Lee, Kibong Kim, Hyunjeong Liew, Sang Hyung Lee, Ju Eun Lee, Hong-In Lee, Yoo-Hun Suh*, Hee-Sung Park*, and David G. Churchill*
    Dopamine and Cu+/2+ Can Induce Oligomerization of α-Synuclein in the Absence of Oxygen: Two Types of Oligomerization Mechanisms for α-Synuclein and Related Cell Toxicity Studies
    Journal of Neuroscience Research, Mar 2014; 92(3):359-368.
    DOI: 10.1002/jnr.23323

  3. Yonghwang Ha, Aerin Yang, Seyoung Lee, Kibong Kim, Hyunjeong Liew, Yoo-Hun Suh*, Hee-Sung Park*, and David G. Churchill*
    Facile "Stop Codon" Method Reveals Elevated Neuronal Toxicity by Discrete S87p-α-Synuclein Oligomers
    Biochemical and Biophysical Research Communications, Jan 2014; 443(3):1085-1091.
    DOI: 10.1016/j.bbrc.2013.12.099

2013

  1. Sangsik Lee, Seunghee Oh, Aerin Yang, Jihyo Kim, Dieter Söll, Daeyoup Lee*, and Hee-Sung Park*
    A Facile Strategy for Selective Incorporation of Phosphoserine into Histones
    Angewandte Chemie International Edition, May 2013; 52(22):5771-5775.
    [Selected as V.I.P. and Front Cover]
    DOI: 10.1002/anie.201300531

2012

  1. Jihyo Kim, Moon-Hyeong Seo, Sangsik Lee, Kyukwang Cho, Aerin Yang, Kyunghwa Woo, Hak-Sung Kim*, and Hee-Sung Park*
    Simple and Efficient Strategy for Site-Specific Dual Labeling of Proteins for Single-Molecule Fluorescence Resonance Energy Transfer Analysis
    Analytical Chemistry, Dec 2012; 85(3):1468-1474.
    DOI: 10.1021/ac303089v

  2. Takuya Umehara, Jihyo Kim, Sangsik Lee, Li-Tao Guo, Dieter Söll*, and Hee-Sung Park*
    N-Acetyl Lysyl-tRNA Synthetases Evolved by a CcdB-based Selection Possess N-Acetyl Lysine Specificity in vitro and in vivo
    FEBS Letters, Mar 2012; 586(6):729-733.
    DOI: 10.1016/j.febslet.2012.01.029

2011

  1. Moon-Hyeong Seo, Tae-Sun Lee, Eunkyung Kim, Young Lag Cho, Hee-Sung Park, Tae-Young Yoon*, and Hak-Sung Kim*
    Efficient Single-Molecule Fluorescence Resonance Energy Transfer Analysis by Site-Specific Dual-Labeling of Protein Using an Unnatural Amino Acid
    Analytical Chemistry, Oct 2011; 83(23):8849-8854.
    DOI: 10.1021/ac202096t

  2. Hee-Sung Park, Michael J. Hohn, Takuya Umehara, Li-Tao Guo, Edith M. Osborne, Jack Benner, Christopher J. Noren*, Jesse Rinehart*, and Dieter Söll*
    Expanding the Genetic Code of Escherichia coli with Phosphoserine
    Science, Aug 2011; 333(6046):1151-1154.
    DOI: 10.1126/science.1207203

  3. Moon-Hyeong Seo, Jieun Han, Zongwen Jin, Dong-Won Lee, Hee-Sung Park*, and Hak-Sung Kim*
    Controlled and Oriented Immobilization of Protein by Site-Specific Incorporation of Unnatural Amino Acid
    Analytical Chemistry, Mar 2011; 83(8):2841-2845.
    DOI: 10.1021/ac103334b

2007

  1. Satwik Kamtekar, Michael J. Hohn, Hee-Sung Park, Michael Schnitzbauer, Anselm Sauerwald, Dieter Söll, and Thomas A. Steitz*
    Toward Understanding Phophoseryl-tRNACys Formation: The Crystal Structure of Methanococcus maripaludis Phosphoseryl-tRNA Synthetase
    Proceedings of the National Academy of Sciences, Feb 2007; 104(8):2620-2625.
    DOI: 10.1073/pnas.0611504104

2006

  1. Michael J. Hohn, Hee-Sung Park, Patrick O’Donoghue, Michael Schnitzbauer, and Dieter Söll*
    Emergence of the Universal Genetic Code Imprinted in an RNA Record
    Proceedings of the National Academy of Sciences, Nov 2006; 103(48):18095-18100.
    DOI: 10.1073/pnas.0608762103

  2. Hee-Sung Park, Sung-Hun Nam, Jin Kak Lee, Chang No Yoon, Bengt Mannervik, Stephen J. Benkovic, and Hak-Sung Kim*
    Design and Evolution of New Catalytic Activity with an Existing Protein Scaffold
    Science, Jan 2006; 311(5760):535-538.
    DOI: 10.1126/science.1118953

2005

  1. Sung-Hun Nam, Hee-Sung Park, and Hak-Sung Kim*
    Evolutionary Relationship and Application of a Superfamily of Cyclic Amidohydrolase Enzymes
    The Chemical Record, Oct 2005; 5(5):298-307.
    DOI: 10.1002/tcr.20057

2004

  1. Hee-Sung Park, Ki-Hoon Oh, and Hak-Sung Kim*
    Improving the Functional Expression of N-Carbamoylase by Directed Evolution using the Green Fluorescent Protein Fusion Reporter System
    Methods in Enzymology, Aug 2004; 388:187-195.
    DOI: 10.1016/S0076-6879(04)88017-0

  2. Young-Hoon Cheon, Hee-Sung Park, Jin-Hyun Kim and Hak-Sung Kim*
    Manipulation of the Active Site Loops of D-Hydantoinase, a (β/α)8-Barrel Protein, for Modulation of the Substrate Specificity
    Biochemistry, May 2004; 43(23):7413-7420.
    DOI: 10.1021/bi036330o

2003

  1. Young-Hoon Cheon, Hee-Sung Park, Sang-Chul Lee, Dong-Eun Lee, and Hak-Sung Kim*
    Structure-based Mutational Analysis of the Active Site Residues of D-Hydantoinase
    Journal of Molecular Catalysis B: Enzymatic, Dec 2003; 26(3-6):217-222.
    DOI: 10.1016/j.molcatb.2003.06.005

2001

  1. Hee-Sung Park, and Hak-Sung Kim*
    Genetic and Structural Organization of the Aminophenol Catabolic Operon and Its Implication for Evolutionary Process
    Journal of Bacteriology, Sep 2001; 183(17):5074-5081.
    DOI: 10.1128/jb.183.17.5074-5081.2001

  2. Geun-Joong Kim, Young-Hoon Cheon, Min-Soon Park, Hee-Sung Park, and Hak-Sung Kim*
    Generation of Protein Lineages with New Sequence Spaces by Functional Salvage Screen
    Protein Engineering, Design and Selection, Sep 2001; 14(9):647-654.
    DOI: 10.1093/protein/14.9.647

2000

  1. Hee-Sung Park and Hak-Sung Kim*
    Identification and Characterization of the Nitrobenzene Catabolic Plasmids pNB1 and pNB2 in Pseudomonas putida HS12
    Journal of Bacteriology, Feb 2000; 182(3):573-580.
    DOI: 10.1128/jb.182.3.573-580.2000

1999

  1. Jang-Young Lee, Hee-Sung Park, and Hak-Sung Kim*
    Adenosylcobalamin-Mediated Methyl Transfer by Toluate cis-Dihydrodiol Dehydrogenase of the TOL Plasmid pWW0
    Journal of Bacteriology, May 1999; 181(9):2953-2957.
    DOI: 10.1128/jb.181.9.2953-2957.1999

  2. Hee-Sung Park, Sung-Jin Lim, Yong Keun Chang, Andrew G. Livingston, and Hak-Sung Kim*
    Degradation of Chloronitrobenzenes by a Coculture of Pseudomonas putida and a Rhodococcus sp
    Applied and Environmental Microbiology, Mar 1999; 65(3):1083-1091.
    DOI: 10.1128/AEM.65.3.1083-1091.1999

1998

  1. Hee-Sung Park, Jang-Young Lee, and Hak-Sung Kim*
    Production of L-DOPA(3,4-Dihydroxyphenyl-L-Alanine) from Benzene by Using a Hybrid Pathway
    Biotechnology and Bioengineering, Apr 1998; 58(2-3):339-343.
    DOI: 10.1002/(SICI)1097-0290(19980420)58:2/3<339::AID-BIT36>3.0.CO;2-4


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