Leng, Fenfei
Contact Info
Overview
overview
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Dr. Leng's laboratory focuses on studying how transcription affects DNA structural changes and activates or inhibits nearby promoters. Using defined protein systems and in vivo E. coli cells, they have found that transcription is a major chromosome remodeling force in bacteria at exponential phase and certain DNA binding proteins, such as FIS and HU, function as topological barriers to modulate localized DNA supercoiling stemming from transcription. We are also utilizing our in vitro and in vivo systems derived from these basic studies to identify or discover antibiotics targeting bacterial DNA gyrase.
A second project in Dr. Leng's laboratory focuses on studies of the mammalian high mobility group protein AT-hook 2 (HMGA2), a nuclear transcription factor associated with many physiological functions including oncogenesis, obesity, stem cell youth, human height, and human intelligence. This protein contains three "AT hook" DNA binding motifs and specifically recognizes the minor groove of AT-rich DNA sequences. They are particularly interested in understanding the structures and functions of this intriguing protein, and hope to use their knowledge from this basic research to discover or identify small molecular compounds to combat cancers by targeting HMGA2-DNA interactions.
Scholarly & Creative Works
selected publications
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Article
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2021A T5 Exonuclease-Based Assay for DNA Topoisomerases and DNA IntercalatorsFull Text via DOI: 10.1021/acsomega.1c00962 Web of Science: 000651520800042
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2021Trapped Ion Mobility Spectrometry of Native Macromolecular Assemblies. ANALYTICAL CHEMISTRY. 93:2933-2941.Full Text via DOI: 10.1021/acs.analchem.0c04556 Web of Science: 000618858500027
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2020Identification of HMGA2 inhibitors by AlphaScreen-based ultra-high-throughput screening assays. SCIENTIFIC REPORTS. 10.Full Text via DOI: 10.1038/s41598-020-75890-0 Web of Science: 000589618700022
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2020R-loops promote trinucleotide repeat deletion through DNA base excision repair enzymatic activities. JOURNAL OF BIOLOGICAL CHEMISTRY. 295:13902-13913.Full Text via DOI: 10.1074/jbc.RA120.014161 Web of Science: 000578444100016
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2019Fis protein forms DNA topological barriers to confine transcription-coupled DNA supercoiling in Escherichia coli. FEBS LETTERS. 594:791-798.Full Text via DOI: 10.1002/1873-3468.13643 Web of Science: 000496346800001
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2019Kinetic Study of DNA Topoisomerases by Supercoiling-Dependent Fluorescence Quenching. ACS OMEGA. 4:18413-18422.Full Text via DOI: 10.1021/acsomega.9b02676 Web of Science: 000495089100048
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2019Mechanism and resistance for antimycobacterial activity of a fluoroquinophenoxazine compound. PLOS ONE. 14.Full Text via DOI: 10.1371/journal.pone.0207733 Web of Science: 000459709100003
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2019Microheterogeneity of Topoisomerase IA/IB and Their DNA-Bound States. ACS OMEGA. 4:3619-3626.Full Text via DOI: 10.1021/acsomega.8b02887 Web of Science: 000460237300126
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2018Inhibition of the gyrA promoter by transcription-coupled DNA supercoiling in Escherichia coli. SCIENTIFIC REPORTS. 8.Full Text via DOI: 10.1038/s41598-018-33089-4 Web of Science: 000446339400043
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2018Differentiating Parallel and Antiparallel DNA Duplexes in the Gas Phase Using Trapped Ion Mobility Spectrometry. JOURNAL OF PHYSICAL CHEMISTRY B. 122.Full Text via DOI: 10.1021/acs.jpcb.7b12544 Web of Science: 000439002900001
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2018Peptide Sequence Influence on the Conformational Dynamics and DNA binding of the Intrinsically Disordered AT-Hook 3 Peptide. SCIENTIFIC REPORTS. 8.Full Text via DOI: 10.1038/s41598-018-28956-z Web of Science: 000438850200030
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2018Tailoring peptide conformational space with organic gas modifiers in TIMS-MS. INTERNATIONAL JOURNAL FOR ION MOBILITY SPECTROMETRY. 21.Full Text via DOI: 10.1007/s12127-018-0231-5 Web of Science: 000432547000005
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2018Protein-mediated loops in supercoiled DNA create large topological domains. NUCLEIC ACIDS RESEARCH. 46.Full Text via DOI: 10.1093/nar/gky153 Web of Science: 000433056900014
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2018Crystal structure and conformational analysis of doxorubicin nitrate. ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS. 74.Full Text via DOI: 10.1107/S2056989018002955 Web of Science: 000426268200029
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2018Protein-mediated looping of DNA under tension requires supercoiling. NUCLEIC ACIDS RESEARCH. 46:2370-2379.
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2017Biochemical and biophysical properties of positively supercoiled DNA. BIOPHYSICAL CHEMISTRY. 230:68-73.
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2017Selective Inhibition of Escherichia coli RNA and DNA Topoisomerase I by Hoechst 33258 Derived Mono- and Bisbenzimidazoles. JOURNAL OF MEDICINAL CHEMISTRY. 60:4904-4922.
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2017Transient and dynamic DNA supercoiling potently stimulates the leu-500 promoter in Escherichia coli. JOURNAL OF BIOLOGICAL CHEMISTRY. 292:14566-14575.
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2016Characterization of an epoxide hydrolase from the Florida red tide dinoflagellate, Karenia brevis. PHYTOCHEMISTRY. 122:11-21.
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2016DNA supercoiling, a critical signal regulating the basal expression of the lac operon in Escherichia coli. SCIENTIFIC REPORTS. 6.
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2016Direct observation of a 91 bp LacI-mediated, negatively supercoiled DNA loop by atomic force microscope. FEBS LETTERS. 590:613-618.
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2016Fluorescently labeled circular DNA molecules for DNA topology and topoisomerases. SCIENTIFIC REPORTS. 6.
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2016RNA topoisomerase is prevalent in all domains of life and associates with polyribosomes in animals. NUCLEIC ACIDS RESEARCH. 44:6335-6349.
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2015A rapid and sensitive high-throughput screening method to identify compounds targeting protein-nucleic acids interactions. NUCLEIC ACIDS RESEARCH. 43.
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2014DNA supercoiling: A regulatory signal for the lambda repressor. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 111:15402-15407.
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2014Selective inhibition of bacterial topoisomerase I by alkynyl-bisbenzimidazoles. MEDCHEMCOMM. 5:816-825.
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2014lsomerization Kinetics of AT Hook Decapeptide Solution Structures. ANALYTICAL CHEMISTRY. 86:1210-1214.
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2013DNA Bending by Proteins: Utilizing Plasmid pBendAT as a Tool. DNA ELECTROPHORESIS: METHODS AND PROTOCOLS. 1054:267-282.
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2013HMGN1 Modulates Nucleosome Occupancy and DNase I Hypersensitivity at the CpG Island Promoters of Embryonic Stem Cells. MOLECULAR AND CELLULAR BIOLOGY. 33:3377-3389.
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2012Determining DNA supercoiling enthalpy by isothermal titration calorimetry. BIOCHIMIE. 94:2665-2672.
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2011A rapid procedure to purify Escherichia coli DNA topoisomerase I. PROTEIN EXPRESSION AND PURIFICATION. 77:214-219.
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2011Dividing a supercoiled DNA molecule into two independent topological domains. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 108:19973-19978.
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2010DNA Bending by the Mammalian High-Mobility Group Protein AT Hook 2. BIOCHEMISTRY. 49:1590-1595.
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2010DNA linking number change induced by sequence-specific DNA-binding proteins. NUCLEIC ACIDS RESEARCH. 38:3643-3654.
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2009Binding the Mammalian High Mobility Group Protein AT-hook 2 to AT-Rich Deoxyoligonucleotides: Enthalpy-Entropy Compensation. BIOPHYSICAL JOURNAL. 96:4144-4152.
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2008Inhibition of high-mobility-group A2 protein binding to DNA by netropsin: A biosensor-surface plasmon resonance assay. ANALYTICAL BIOCHEMISTRY. 374:7-15.
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2007Large scale preparation of the mammalian high mobility group protein A2 for biophysical studies. PROTEIN AND PEPTIDE LETTERS. 14:87-91.
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2007Specific recognition of AT-Rich DNA sequences by the mammalian high mobility group-protein AT-hook 2: A SELEX study. BIOCHEMISTRY. 46:13059-13066.
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2007Transcription-coupled hypernegative supercoiling of plasmid DNA by T7 RNA polymerase in Escherichia coli topoisomerase I-deficient strains. JOURNAL OF MOLECULAR BIOLOGY. 374:925-935.
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2005Energetics of binding the mammalian high mobility group protein HMGA2 to poly(dA-dT)(2) and poly(dA)-poly(dT). JOURNAL OF MOLECULAR BIOLOGY. 352:629-645.
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2004Coupling DNA supercoiling to transcription in defined protein systemsFull Text via DOI: 10.1074/jbc.M403798200
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2003Energetics of echinomycin binding to DNA. NUCLEIC ACIDS RESEARCH. 31.Full Text via DOI: 10.1093/nar/gkg826 Web of Science: 000186312300023
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1998Chemical cross-linking of ethidium to DNA by glyoxalFull Text via DOI: 10.1016/S0167-4781(98)00122-5
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1996Base specific and regioselective chemical cross-linking of daunorubicin to DNAFull Text via DOI: 10.1021/ja9542606
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Correction
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2018HMGN1 Modulates Nucleosome Occupancy and DNase I Hypersensitivity at the CpG Island Promoters of Embryonic Stem Cells (vol 33, pg 337, 2013). MOLECULAR AND CELLULAR BIOLOGY.Full Text via DOI: 10.1128/MCB.00185-18 Web of Science: 000433419600004
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Meeting Abstract
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2019Insights on the structural integrity of knot proteins using trapped ion mobility spectrometry - mass spectrometry. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY.Web of Science: 000478860500229
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2019Tight Binding of Natural Polyphenols to the Intrinsically Disordered Mammalian High Mobility Group Protein At-Hook 2. BIOPHYSICAL JOURNAL. 482A-482A.Web of Science: 000460779802421
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2018Identification of Suramin as a Potent and Specific Inhibitor of the Mammalian High Mobility Group Protein at-Hook 2 (HMGA2)-DNA Interactions. BIOPHYSICAL JOURNAL.Web of Science: 000430450000709
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2017Chemical cross-linking of doxorubicin to synthetic oligonucleotides by formaldehyde. FASEB JOURNAL.Web of Science: 000405461402327
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2017Protein-Mediated Loops in Supercoiled DNA Create Large Topological Domains. BIOPHYSICAL JOURNAL. 170A-170A.Full Text via DOI: 10.1016/j.bpj.2016.11.938 Web of Science: 000402328000837
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2016Design and Construct a Type of Fluorescently Labeled Circular DNA Molecules to Study DNA Topology and Topoisomerases by Fluorescence Resonance Energy Transfer (FRET). BIOPHYSICAL JOURNAL. 564A-564A.Full Text via DOI: 10.1016/j.bpj.2015.11.3019 Web of Science: 000375143000250
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2016Effect of FIS on Transcription-Coupled DNA Supercoiling in E. coli. BIOPHYSICAL JOURNAL. 233A-234A.Full Text via DOI: 10.1016/j.bpj.2015.11.1287 Web of Science: 000375141600138
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2016HU Protein and DNA Supercoiling Dramatically Enhance Lac-Repressor-Mediated DNA Looping. BIOPHYSICAL JOURNAL. 236A-236A.Full Text via DOI: 10.1016/j.bpj.2015.11.1302 Web of Science: 000375141600151
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2014Activating the Prokaryotic leu-500 Promoter by Transient, Dynamic DNA Supercoiling in Escherichia Coli. BIOPHYSICAL JOURNAL. 487A-488A.Full Text via DOI: 10.1016/j.bpj.2013.11.4476 Web of Science: 000337000402702
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2014Biochemical and Biophysical Properties of Positively Supercoiled DNA. BIOPHYSICAL JOURNAL. 66A-66A.Full Text via DOI: 10.1016/j.bpj.2013.11.444 Web of Science: 000337000400340
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2013Lactose Repressor Functions as a DNA Topological Barrier in Escherichia Coli Lactose Operon. BIOPHYSICAL JOURNAL. 417A-418A.Full Text via DOI: 10.1016/j.bpj.2012.11.2326 Web of Science: 000316074304126
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2009Protein-Induced DNA Unwinding is An Intrinsic Feature of Certain Sequence-Specific DNA-Binding Proteins. BIOPHYSICAL JOURNAL. 414A-414A.Web of Science: 000426354000211
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2007Binding the mammalian high mobility group protein AT-hook 2 to AT-rich deoxyoligonucleotides: enthalpy-entropy compensation. BIOPHYSICAL JOURNAL. 233A-233A.Web of Science: 000243972401296
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2007The Mammalian high mobility group protein AT-hook 2 (HMGA2) is a sequence-specific DNA-binding protein. BIOPHYSICAL JOURNAL. 55A-55A.Web of Science: 000243972400255
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2006A new method to purify the Mammalian High Mobility Group Protein HGMA2. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY.Web of Science: 000238125901627
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2005Energetics of mammalian high mobility group protein HMGA2 recognizing DNA minor groove. BIOPHYSICAL JOURNAL. 62A-62A.Web of Science: 000226378500306
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Review
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2020The Mammalian High Mobility Group Protein AT-Hook 2 (HMGA2): Biochemical and Biophysical Properties, and Its Association with Adipogenesis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES.Full Text via DOI: 10.3390/ijms21103710 Web of Science: 000539312100306
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2016Protein-induced DNA linking number change by sequence-specific DNA binding proteins and its biological effects. 197-207.Full Text via DOI: 10.1007/s12551-016-0204-z
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2013Transcription-coupled DNA supercoiling in defined protein systems and in E. coli topA mutant strains. IUBMB LIFE. 615-622.
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chaired theses and dissertations
- Zhi, Xiaoduo, Transcription-Coupled DNA Supercoiling in Escherichia Coli: Mechanisms and Biological Functions 2012
- Xu, Xiaozhou, Kinetics of E. coli Topoisomerase I and Energetic Studies of DNA Supercoiling by Isothermal Titration Calorimetry 2010
- Cui, Tengjiao, Specific binding of mammalian high mobility group protein at-hook 2 to the minor groove of at-rich DNAS : thermodynamic and specificity studies 2007
- Edwards, Lorraine Katy, Biochemical characterization of mammalian high mobility group protein A2 2006
Research
research interests
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Transcription-Coupled DNA Supercoiling
Protein-DNA Interactions
principal investigator on
- Targeting transcription-coupled DNA supercoiling for discovering antibiotics against bacterial DNA gyrase awarded by National Institutes of Health 2017 - 2019
- Transcription-coupled DNA Supercoiling awarded by National Institutes of Health 2014 - 2018
- DOR Bridge Funding awarded by FIU Division of Research 2013 - 2014
- Mechanisms of Transcription-Coupled DNA Supercoiling awarded by Eunice Kennedy Shriver National Institute of Child Health and Human Development 2009 - 2014
co-principal investigator on
investigator on
Teaching
teaching activities
- BCH7930-U01: Biochemistry Graduate Seminar Spring Term 2019
- CHM4304-U02: Biological Chemistry I Fall Term 2019
- CHM4910-U03: Undergraduate Research in Chemistry Spring Term 2019
- CHM4910-U14: Undergraduate Research in Chemistry Fall Term 2019
- CHM7910-U15: Dissertation Research Fall Term 2019
- CHM7980-U02: PH.D. Dissertation Fall Term 2019
- CHM7980-U13: PH.D. Dissertation Spring Term 2019
Contact
full name
- Fenfei Leng
visualizations
Recent publications and grants in Scholars@FIU
publication subject areas
Citation index-derived subject areas the researcher has published in