Article
Biology
Raymond F. Pauszek, Rajan Lamichhane, Arishma Rajkarnikar Singh, David P. Millar
Summary: The study using single-molecule FRET microscopy revealed that the 5' nuclease domain in DNA polymerase I (Pol I) from Escherichia coli adopts different positions within Pol I-DNA complexes depending on the nature of the DNA substrate, indicating the structural dynamics underlying functional coordination in Pol I.
Article
Biochemistry & Molecular Biology
William C. Hacker, Adrian H. Elcock
Summary: Stochastic simulation models have been instrumental in understanding the mechanisms behind prokaryotic transcription and translation. However, most models have focused only on one process and have not incorporated high-throughput sequencing data. We have developed spotter, a simulation model that combines detailed representations of prokaryotic transcription, translation, and DNA supercoiling, and integrates single-molecule experimental data with cellular-scale data.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Oleksii Zdorevskyi, Amina Djurabekova, Jonathan Lasham, Vivek Sharma
Summary: Respiratory complex I is an redox-driven proton pump that contributes to mitochondrial ATP generation. The recent cryo-EM structural data revealed the positions of water molecules in the membrane domain of the complex, but the flow of protons in the membrane-bound subunits is still unclear. Computer simulations on high-resolution structural data show that protons can travel through the antiporter-like subunits, including at the subunit-subunit interface parallel to the membrane. Our simulations also demonstrate the role of conserved tyrosine residues and electrostatic effects in facilitating proton transfer. These results challenge prevailing proton pumping models of respiratory complex I.
Article
Biochemistry & Molecular Biology
Alicia M. Crisalli, Yi-Tzai Chen, Ang Cai, Deyu Li, Bongsup P. Cho
Summary: This study investigates the impact of epigenetic modulation on conformational heterogeneity and bypass of DNA lesions in different sequence contexts. The results reveal that the bypass efficiency of DNA damage varies depending on the sequence context, particularly in sequences with 5mC modification. The conformational basis behind these variations differs between different sequence contexts, providing novel insights into how epigenetic modifications affect the repair of DNA adducts.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Medicinal
Clement Monsarrat, Guillaume Compain, Christophe Andre, Sylvain Engilberge, Isabelle Martiel, Vincent Olieric, Philippe Wolff, Karl Brillet, Marie Landolfo, Cyrielle Silva da Veiga, Jerome Wagner, Gilles Guichard, Dominique Y. Burnouf
Summary: A study was conducted on a series of peptides interacting with the Escherichia coli SC binding pocket, showing improved affinity through various modifications. X-ray structure analysis revealed new peptide-protein interactions that explained the enhanced binding mechanism.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Avik Mukherjee, Jade Ealy, Yanqing Huang, Nina Catherine Benites, Mark Polk, Markus Basan
Summary: Utilizing a combination of experiments and computer simulations, researchers have found that the emergence and persistence of coexistence of multiple ecotypes in Escherichia coli long-term evolution experiment can be explained by two interacting trade-offs rooted in biochemical constraints. Faster growth enabled by higher fermentation and obligate acetate excretion results in longer lag times when utilizing acetate after glucose is depleted, creating an ecological niche for a slower-growing ecotype specialized in switching to acetate. These findings highlight the importance of trade-offs in the evolution of complex microbial communities.
NATURE COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Dongdong Zhao, Ju Li, Siwei Li, Xiuqing Xin, Muzi Hu, Marcus A. Price, Susan J. Rosser, Changhao Bi, Xueli Zhang
Summary: This study presents new glycosylase base editors (GBEs) that can induce C-to-A and C-to-G transversions in bacteria and mammalian cells, respectively. The GBEs can serve as a complement to existing adenine and cytidine base editors (ABE and CBE) and have the potential to target G/C disease-causing mutations.
NATURE BIOTECHNOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Dongdong Zhao, Ju Li, Siwei Li, Xiuqing Xin, Muzi Hu, Marcus A. Price, Susan J. Rosser, Changhao Bi, Xueli Zhang
Summary: The study introduces novel glycosylase base editors (GBEs) that can induce C-to-A and C-to-G transversions in Escherichia coli and mammalian cells, respectively. The new editors exhibit high editing specificity and efficiency, making them potential tools for targeting G/C disease-causing mutations.
NATURE BIOTECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jia Yi, Zhengjun Cai, Haipeng Qiu, Feihu Lu, Zhiteng Luo, Bingyi Chen, Qiong Gu, Jun Xu, Huihao Zhou
Summary: Methionyl-tRNA synthetase (MetRS) is an essential enzyme that charges tRNA(Met) with l-methionine (L-Met) to decode the ATG codon for protein translation. Crystal structures of a representative MetRS1 from Staphylococcus aureus (SaMetRS) were reported, revealing differences in structural organization and dynamic movement compared to human cytosolic MetRS (HcMetRS, or MetRS2). Screening of chemical fragments against SaMetRS identified ten hits that bound to either the L-Met binding site or an auxiliary pocket near the tRNA binding site. Interestingly, fragment binding was enhanced by ATP in most cases, suggesting a potential ATP-assisted ligand binding mechanism in MetRS1. The findings inspire the development of new MetRS1 inhibitors for fighting microbial infections.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Carol S. Henger, Dyan J. Straughan, Charles C. Y. Xu, Batya R. Nightingale, Heidi E. Kretser, Mary K. Burnham-Curtis, Denise McAloose, Tracie A. Seimon
Summary: All species of big cats are protected under international regulations due to population declines caused by poaching and illegal trade in their products. A rapid qPCR test has been developed to identify and differentiate DNA from six big cat species in wildlife products, with high efficiency, sensitivity, and specificity. This test can be used as a screening method to combat illegal trade in big cats, benefiting their conservation efforts globally.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Yuhe Kan, Zhaoyang Jin, Yongqi Ke, Dao Lin, Liang Yan, Li Wu, Yujian He
Summary: L-nucleosides have effects on DNA replication, and their bypass and mutagenic effects vary depending on the nucleoside. This study investigated the impact of L-deoxynucleosides on recombinant DNA replication using restriction enzyme-mediated assays, and performed molecular dynamics simulations to explore the effects of DNA polymerase. These findings provide insights into the cytotoxic and mutagenic properties of L-nucleoside drugs.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Camille Mumm, Melissa L. Drexel, Torrin L. McDonald, Adam G. Diehl, Jessica A. Switzenberg, Alan P. Boyle
Summary: Recombinant plasmid vectors are versatile tools that have facilitated discoveries in various fields. However, errors can be introduced during the process of creating recombinant DNA, making sequence validation essential. While Sanger sequencing is the current standard for plasmid validation, it has limitations in sequencing complex secondary structures and scaling for full-plasmid sequencing. This article introduces OnRamp, an alternative method that combines the advantages of high-throughput sequencing and Sanger sequencing by leveraging nanopore's long-read sequencing technology. It provides customized wet-lab protocols and an analysis pipeline for plasmid preparation and data processing, aiming to make long-read sequencing more accessible for routine plasmid validation.
Article
Multidisciplinary Sciences
Radhika Malik, Robert E. Johnson, Louise Prakash, Satya Prakash, Iban Ubarretxena-Belandia, Aneel K. Aggarwal
Summary: The study investigates the structure of the DNA-Pol zeta complex and its ability to extend DNA synthesis past mismatched base pairs. The results reveal the conformational changes in the Pol zeta active site and how it responds to mismatched DNA, allowing for the proper binding and extension of nucleotides. This study provides valuable insights into the regulation of DNA synthesis in eukaryotes.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Jiashen Zhou, Lin Zhang, Liping Zeng, Lu Yu, Yuanyuan Duan, Siqi Shen, Jingyan Hu, Pan Zhang, Wenyan Song, Xiaoxue Ruan, Jing Jiang, Yinan Zhang, Lu Zhou, Jia Jia, Xudong Hang, Changlin Tian, Houwen Lin, Hong-Zhuan Chen, John E. Cronan, Hongkai Bi, Liang Zhang
Summary: The study presents the crystal structures of the essential UFA biosynthesis enzyme FabX in Helicobacter pylori, revealing a unique [4Fe-4S] cluster that potentiates FMN oxidation during dehydrogenase catalysis. This [4Fe-4S] cluster is crucial for unsaturated fatty acid synthesis and contributes to the pathogenic function of H. pylori in the corrosion of gastric mucosa.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Xiao-Ping Li, Rajesh K. Harijan, Bin Cao, Jennifer N. Kahn, Michael Pierce, Anastasiia M. Tsymbal, Jacques Y. Roberge, David Augeri, Nilgun E. Tumer
Summary: In this study, a new strategy was used to disrupt RTA-ribosome interactions and improve the affinity and inhibitory activity of small-molecular-weight lead compounds by fragment screening and structure-guided approaches. The lead compounds were further optimized to obtain improved compounds with over an order of magnitude higher efficiency, which bind at the RTA-ribosome binding site in a distinctive manner and inhibit ricin activity by causing local conformational changes without altering the catalytic site geometry. These compounds represent the first agents that can protect against ricin holotoxin by acting directly on RTA.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Xiumei Huang, Edward A. Motea, Zachary R. Moore, Jun Yao, Ying Dong, Gaurab Chakrabarti, Jessica A. Kilgore, Molly A. Silvers, Praveen L. Patidar, Agnieszka Cholka, Farjana Fattah, Yoonjeong Cha, Glenda G. Anderson, Rebecca Kusko, Michael Peyton, Jingsheng Yan, Xian-Jin Xie, Venetia Sarode, Noelle S. Williams, John D. Minna, Muhammad Beg, David E. Gerber, Erik A. Bey, David A. Boothman
Article
Biochemistry & Molecular Biology
Praveen L. Patidar, Edward A. Motea, Farjana J. Fattah, Yunyun Zhou, Julio C. Morales, Yang Xie, Harold R. Garner, David A. Boothman
NUCLEIC ACIDS RESEARCH
(2016)
Article
Genetics & Heredity
Julio C. Morales, Patricia Richard, Praveen L. Patidar, Edward A. Motea, Tuyen T. Dang, James L. Manley, David A. Boothman
Article
Oncology
Jung-Suk Choi, Seol Kim, Edward Motea, Anthony Berdis
Article
Biochemistry & Molecular Biology
Lifen Cao, Long Shan Li, Christopher Spruell, Ling Xiao, Gaurab Chakrabarti, Erik A. Bey, Kathryn E. Reinicke, Melissa C. Srougi, Zachary Moore, Ying Dong, Peggy Vo, Wareef Kabbani, Chin-Rang Yang, Xiaoyu Wang, Farjana Fattah, Julio C. Morales, Edward A. Motea, William G. Bornmann, John S. Yordy, David A. Boothman
ANTIOXIDANTS & REDOX SIGNALING
(2014)
Article
Biochemistry & Molecular Biology
Julio C. Morales, Patricia Richard, Amy Rommel, Farjana J. Fattah, Edward A. Motea, Praveen L. Patidar, Ling Xiao, Konstantin Leskov, Shwu-Yuan Wu, Walter N. Hittelman, Cheng-Ming Chiang, James L. Manley, David A. Boothman
NUCLEIC ACIDS RESEARCH
(2014)
Review
Biochemistry & Molecular Biology
Xiaofei Chen, Jade Mims, Xiumei Huang, Naveen Singh, Edward Motea, Sarah M. Planchon, Muhammad Beg, Allen W. Tsang, Mercedes Porosnicu, Melissa L. Kemp, David A. Boothman, Cristina M. Furdui
ANTIOXIDANTS & REDOX SIGNALING
(2018)
Article
Oncology
Edward A. Motea, Xiumei Huang, Naveen Singh, Jessica A. Kilgore, Noelle S. Williams, Xian-Jin Xie, David E. Gerber, Muhammad S. Beg, Erik A. Bey, David A. Boothman
CLINICAL CANCER RESEARCH
(2019)
Review
Oncology
Naveen Singh, S. Louise Pay, Snehal B. Bhandare, Udhaya Arimpur, Edward A. Motea
Article
Multidisciplinary Sciences
Praveen L. Patidar, Talysa Viera, Julio C. Morales, Naveen Singh, Edward A. Motea, Megha Khandelwal, Farjana J. Fattah
SCIENTIFIC REPORTS
(2020)
Review
Oncology
Colton L. Starcher, S. Louise Pay, Naveen Singh, I-Ju Yeh, Snehal B. Bhandare, Xiaolin Su, Xiumei Huang, Erik A. Bey, Edward A. Motea, David A. Boothman
FRONTIERS IN ONCOLOGY
(2020)
Article
Cell Biology
Rachel A. Caston, Fenil Shah, Colton L. Starcher, Randall Wireman, Olivia Babb, Michelle Grimard, Jack McGeown, Lee Armstrong, Yan Tong, Roberto Pili, Joseph Rupert, Teresa A. Zimmers, Adily N. Elmi, Karen E. Pollok, Edward A. Motea, Mark R. Kelley, Melissa L. Fishel
Summary: This study investigates the synergistic effect of dual targeting Ref-1 and STAT3 pathways in cancer, showing promising results in inhibiting tumor growth and improving tumor response by hindering crosstalk between tumor and its microenvironment.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Ashan P. Wettasinghe, Naveen Singh, Colton L. Starcher, Chloe C. DiTusa, Zakari Ishak-Boushaki, Dimithree Kahanda, Reema McMullen, Edward A. Motea, Jason D. Slinker
Summary: In this study, electrochemical DNA devices were used to quantify and understand the cancer-specific DNA-damaging activity of an emerging drug at extremely low concentrations. The results demonstrated the high potency and selectivity of the drug for NQO1+ cancer cells, and highlighted the potential of these devices in identifying promising drugs requiring improved cell permeability.
Article
Engineering, Biomedical
Yunfeng Yan, Kejin Zhou, Hu Xiong, Jason B. Miller, Edward A. Motea, David A. Boothman, Li Liu, Daniel J. Siegwart
Article
Oncology
Edward A. Motea, Farjana J. Fattah, Ling Xiao, Luc Girard, Amy Rommel, Julio C. Morales, Praveen Patidar, Yunyun Zhou, Andrew Porter, Yang Xie, John D. Minna, David A. Boothman
CLINICAL CANCER RESEARCH
(2018)