Article
Biochemistry & Molecular Biology
Mark A. Nakasone, Karolina A. Majorek, Mads Gabrielsen, Gary J. Sibbet, Brian O. Smith, Danny T. Huang
Summary: This study elucidates the mechanism of processive K48-linked polyUb chain formation by UBE2K, including acceptor Ub recognition and multivalent Ub-binding feature.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Gaku Akimoto, Arianna P. Fernandes, Jeffrey W. Bode
Summary: Ubiquitylation is a process that attaches ubiquitin to proteins in eukaryotic cells and involves multiple enzymes. We have developed a method to transfer ubiquitin specifically to target proteins, which is important for studying protein function.
ACS CENTRAL SCIENCE
(2022)
Article
Chemistry, Medicinal
Steven P. Langston, Stephen Grossman, Dylan England, Roushan Afroze, Neil Bence, Douglas Bowman, Nancy Bump, Ryan Chau, Bei-Ching Chuang, Christopher Claiborne, Larry Cohen, Kelly Connolly, Matthew Duffey, Nitya Durvasula, Scott Freeze, Melissa Gallery, Katherine Galvin, Jeffrey Gaulin, Rachel Gershman, Paul Greenspan, Jessica Grieves, Jianping Guo, Nanda Gulavita, Shumet Hailu, Xingyue He, Kara Hoar, Yongbo Hu, Zhigen Hu, Mitsuhiro Ito, Mi-Sook Kim, Scott Weston Lane, David Lok, Anya Lublinsky, William Mallender, Charles McIntyre, James Minissale, Hirotake Mizutani, Miho Mizutani, Nina Molchinova, Koji Ono, Ashok Patil, Mark Qian, Jessica Riceberg, Vaishali Shindi, Michael D. Sintchak, Keli Song, Teresa Soucy, Yana Wang, He Xu, Xiaofeng Yang, Agatha Zawadzka, Ji Zhang, Sai M. Pulukuri
Summary: SUMOylation is a reversible post-translational modification that involves a cascaded enzymatic process and ATP-dependent activation, regulating protein function by attaching SUMO proteins covalently. TAK-981 is a mechanism-based inhibitor of SAE, optimized for selectivity against related enzymes and prolonged mean residence time of the inhibitory adduct, leading to potent cellular pathway inhibition and ultimately high efficacy in preclinical tumor models, resulting in the identification of the clinical molecule TAK-981.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Chaodong Xiong, Lina Zhou, Jing Tan, Shanshan Song, Xubin Bao, Ning Zhang, Huaqian Ding, Jiannan Zhao, Jin-Xue He, Ze-Hong Miao, Ao Zhang
Summary: NEDD8 plays a crucial role in the functional maintenance and homeostasis of cells, with dysregulation implicated in various human diseases. Therefore, developing new NAE inhibitors with high potency and better safety profiles is urgently needed.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Lian Yang, Qing Zhang, Yili Yang, Qun Wang
Summary: The study investigated the therapeutic effects of PYR-41 on atopic dermatitis. The results showed that PYR-41 can activate the NF-?B signaling pathway by reducing the ubiquitination levels of specific molecules and inhibiting the degradation of I?Ba. In addition, in a mouse model, PYR-41 treatment significantly improved symptoms and reduced the expression of inflammatory markers.
Review
Pharmacology & Pharmacy
Samir H. Barghout, Aaron D. Schimmer
Summary: This article discusses the importance of E1 enzymes in cell biology, particularly their potential role in cancer therapy. Various inhibitors targeting E1 enzymes such as UBA1, SAE, and NAE have been identified, with significant potential in cancer research.
PHARMACOLOGICAL REVIEWS
(2021)
Article
Biochemical Research Methods
Areti-Maria Vasilogianni, Eman El-Khateeb, Brahim Achour, Sarah Alrubia, Amin Rostami-Hodjegan, Jill Barber, Zubida M. Al-Majdoub
Summary: The study developed a family of QconCAT standards for the quantification of pharmacological target proteins in human tissues. These standards showed high purity, high labeling efficiency, and high sequence coverage. These standards are widely used for the quantification of pharmacokinetic and pharmacodynamic targets, and are of great importance in drug research.
JOURNAL OF PROTEOMICS
(2022)
Article
Food Science & Technology
Huan Li, Tianshu Li, Yanbo Wang, Shuifeng Zhang, Huadong Sheng, Linglin Fu
Summary: An accurate and reliable method using stable isotope-labeled internal standard was developed to quantify the primary allergenic proteins in crustaceans. The method showed high accuracy and precision and was successfully applied to commercial food samples.
Article
Chemistry, Applied
Shuying Han, Zhiye Yan, Xiaozheng Huang, Shuo Cai, Ming Zhao, Yunfeng Zheng, Xiao Liu, Haokun Xu, Yu Xie, Rong Hou, Jin-Ao Duan, Rui Liu
Summary: In this study, a new strategy utilizing response-boosting was developed to enhance detection sensitivity for the absolute quantification of gelatin in Asini Corii Colla, a commonly used food therapy product in Asia. Peptidomics analysis and isotope-labeled internal standard were used to compensate for matrix effects and construct matrix-matched calibration curves. The established method showed good reliability and sensitivity for absolute quantification of gelatin peptides.
Article
Biochemical Research Methods
Benjamin J. Sanchez, Petri-Jaan Lahtvee, Kate Campbell, Sergo Kasvandik, Rosemary Yu, Ivan Domenzain, Aleksej Zelezniak, Jens Nielsen
Summary: Protein quantification via label-free mass spectrometry is a popular method for predicting genome-wide absolute protein abundances, but suffers from poor technical reproducibility. This study demonstrates that a simple normalization and rescaling approach can perform as accurately, yet more precisely, than methods relying on external standards. Additionally, it shows that inter-batch reproducibility is worse than biological reproducibility for all evaluated methods, providing a new benchmark for assessing MS data quality for protein quantification.
Article
Biochemical Research Methods
Akshada Gajbhiye, Atakan Nalbant, Tiaan Heunis, Frances Sidgwick, Andrew Porter, Yusri Taha, Matthias Trost
Summary: This study developed a rapid and high-throughput method for the detection of SARS-CoV-2 using isotopically labeled synthetic peptides for absolute quantification. The results showed that the method was able to detect positive patients with high viral load in a short time and quantify patients with Ct values as low as 17.8.
JOURNAL OF PROTEOMICS
(2022)
Article
Biochemical Research Methods
Donatien Lefebvre, Francois Fenaille, Deborah Merda, Kevin Blanco-Valle, Cecile Feraudet-Tarisse, Stephanie Simon, Jacques-Antoine Hennekinne, Yacine Nia, Francois Becher
Summary: This study highlights the importance of improving the sensitivity of top-down mass spectrometry for the identification, differentiation, and absolute quantification of SEA sequence variants. By utilizing immunoaffinity enrichment, a protein internal standard, and optimized acquisition conditions, the top-down method demonstrated efficient identification and precise quantification of SEA variants, as well as providing a supplementary specificity criterion for quantification. The successful evaluation on enterotoxin-producing strains isolated during food poisoning outbreaks showcases the potential of top-down mass spectrometry in complementing traditional methods for toxin analysis.
JOURNAL OF PROTEOME RESEARCH
(2022)
Review
Spectroscopy
Juan J. Calvete, Bruno Lomonte, Anthony J. Saviola, Francisco Calderon Celis, Jorge Ruiz Encinar
Summary: The advent of soft ionization mass spectrometry-based proteomics in the 1990s allowed for integral analysis of whole proteomes. However, the analytical technique itself is inherently nonquantitative, leading to the development of strategies for proteomic quantification. The combination of elemental and molecular mass spectrometry systems holds potential for absolute quantification in various areas of proteomics.
MASS SPECTROMETRY REVIEWS
(2023)
Article
Chemistry, Analytical
Wouter C. Knol, Quincy L. de Vries, Ton Brooijmans, Till Gruendling, Bob W. J. Pirok, Ron A. H. Peters
Summary: Size-exclusion chromatography (SEC) coupled with pyrolysis-gas chromatography (Py-GC) is a powerful tool for polymer analysis. However, the long analysis times of the Py-GC step limit its wider application. Therefore, an online hyphenated SECxPy-MS/FID method was developed, removing the need for GC separation and significantly reducing the second-dimension analysis time compared to SEC-Py-GC. The developed method showed no molar mass discrimination for masses above +/- 1.3 kDa, making it applicable to most commercial polymer systems. Multiple samples, including a complex industrial sample, were successfully analyzed using this method, providing information on chemical composition heterogeneity and molar mass distribution.
ANALYTICA CHIMICA ACTA
(2023)
Article
Virology
Yulia Alejandra Flores-Martinez, Vu Thuy Khanh Le-Trilling, Mirko Trilling
Summary: Human cytomegalovirus manipulates the proteome of infected cells through the ubiquitin proteasome pathway, with the Nedd8-activating enzyme (NAE) being indispensable for neddylation. The drug MLN4924 shows potent antiviral activity against cytomegaloviruses by inactivating CRL, but may have off-target effects due to its nucleoside analog nature. NAE, the neddylation process, and CRLs are potential druggable host dependency factors (HDFs) for cytomegaloviruses.
Article
Biochemistry & Molecular Biology
Tatos Akopian, Olga Kandror, Christopher Tsu, Jack H. Lai, Wengen Wu, Yuxin Liu, Peng Zhao, Annie Park, Lisa Wolf, Lawrence R. Dick, Eric J. Rubin, William Bachovchin, Alfred L. Goldberg
JOURNAL OF BIOLOGICAL CHEMISTRY
(2015)
Article
Toxicology
Vilmos Csizmadia, Paul Hales, Christopher Tsu, Jingya Ma, Jiejin Chen, Pooja Shah, Paul Fleming, Joseph J. Senn, Vivek J. Kadambi, Larry Dick, Francis S. Wolenski
TOXICOLOGY RESEARCH
(2016)
Article
Biochemistry & Molecular Biology
Xingyue He, Jessica Riceberg, Teresa Soucy, Erik Koenig, James Minissale, Melissa Gallery, Hugues Bernard, Xiaofeng Yang, Hua Liao, Claudia Rabino, Pooja Shah, Kristina Xega, Zhong-hua Yan, Mike Sintchak, John Bradley, He Xu, Matt Duffey, Dylan England, Hirotake Mizutani, Zhigen Hu, Jianping Guo, Ryan Chau, Lawrence R. Dick, James E. Brownell, John Newcomb, Steve Langston, Eric S. Lightcap, Neil Bence, Sai M. Pulukuri
NATURE CHEMICAL BIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Marc L. Hyer, Michael A. Milhollen, Jeff Ciavarri, Paul Fleming, Tary Traore, Darshan Sappal, Jessica Huck, Judy Shi, James Gavin, Jim Brownell, Yu Yang, Bradley Stringer, Robert Griffin, Frank Bruzzese, Teresa Soucy, Jennifer Duffy, Claudia Rabino, Jessica Riceberg, Kara Hoar, Anya Lublinsky, Saurabh Menon, Michael Sintchak, Nancy Bump, Sai M. Pulukuri, Steve Langston, Stephen Tirrell, Mike Kuranda, Petter Veiby, John Newcomb, Ping Li, Jing Tao Wu, Josh Powe, Lawrence R. Dick, Paul Greenspan, Katherine Galvin, Mark Manfredi, Chris Claiborne, Benjamin S. Amidon, Neil F. Bence
Article
Biochemistry & Molecular Biology
Henrike C. Besche, Zhe Sha, Nikolay V. Kukushkin, Andreas Peth, Eva-Maria Hock, Woong Kim, Steven Gygi, Juan A. Gutierrez, Hua Liao, Lawrence Dick, Alfred L. Goldberg
Article
Biochemistry & Molecular Biology
James M. Gavin, Kara Hoar, Qing Xu, Jingya Ma, Yafang Lin, Jiejin Chen, Wei Chen, Frank J. Bruzzese, Sean Harrison, William D. Mallender, Nancy J. Bump, Michael D. Sintchak, Neil F. Bence, Ping Li, Lawrence R. Dick, Alexandra E. Gould, Jesse J. Chen
JOURNAL OF BIOLOGICAL CHEMISTRY
(2014)
Article
Chemistry, Multidisciplinary
Hao Li, Christopher Tsu, Christopher Blackburn, Gang Li, Paul Hales, Lawrence Dick, Matthew Bogyo
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2014)
Article
Multidisciplinary Sciences
Xingyue He, Jessica Riceberg, Sai M. Pulukuri, Steve Grossman, Vaishali Shinde, Pooja Shah, James E. Brownell, Larry Dick, John Newcomb, Neil Bence
Article
Multidisciplinary Sciences
Jessica L. Bridgford, Stanley C. Xie, Simon A. Cobbold, Charisse Flerida A. Pasaje, Susann Herrmann, Tuo Yang, David L. Gillett, Lawrence R. Dick, Stuart A. Ralph, Con Dogovski, Natalie J. Spillman, Leann Tilley
NATURE COMMUNICATIONS
(2018)
Article
Chemistry, Medicinal
Stanley C. Xie, David L. Gillett, Natalie J. Spillman, Christopher Tsu, Madeline R. Luth, Sabine Ottilie, Sandra Duffy, Alexandra E. Gould, Paul Hales, Benjamin A. Seager, Carlie L. Charron, Frank Bruzzese, Xiaofeng Yang, Xiansi Zhao, Shih-Chung Huang, Craig A. Hutton, Jeremy N. Burrows, Elizabeth A. Winzeler, Vicky M. Avery, Lawrence R. Dick, Leann Tilley
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Microbiology
Stanley C. Xie, Riley D. Metcalfe, Eric Hanssen, Tuo Yang, David L. Gillett, Andrew P. Leis, Craig J. Morton, Michael J. Kuiper, Michael W. Parker, Natalie J. Spillman, Wilson Wong, Christopher Tsu, Lawrence R. Dick, Michael D. W. Griffin, Leann Tilley
NATURE MICROBIOLOGY
(2019)
Review
Pharmacology & Pharmacy
Stanley C. Xie, Lawrence R. Dick, Alexandra Gould, Stephen Brand, Leann Tilley
EXPERT OPINION ON THERAPEUTIC TARGETS
(2019)
Article
Multidisciplinary Sciences
Fazal Shirazi, Richard J. Jones, Ram K. Singh, Jianxuan Zou, Isere Kuiatse, Zuzana Berkova, Hua Wang, Hans C. Lee, Samuel Hong, Larry Dick, Nibedita Chattopadhyay, Robert Z. Orlowski
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Multidisciplinary Sciences
Stanley C. Xie, Riley D. Metcalfe, Hirotake Mizutani, Tanya Puhalovich, Eric Hanssen, Craig J. Morton, Yawei Du, Con Dogovski, Shih-Chung Huang, Jeffrey Ciavarri, Paul Hales, Robert J. Griffin, Lawrence H. Cohen, Bei-Ching Chuang, Sergio Wittlin, Ioanna Deni, Tomas Yeo, Kurt E. Ward, Daniel C. Barry, Boyin Liu, David L. Gillett, Benigno F. Crespo-Fernandez, Sabine Ottilie, Nimisha Mittal, Alisje Churchyard, Daniel Ferguson, Anna Caroline C. Aguiar, Rafael V. C. Guido, Jake Baum, Kirsten K. Hanson, Elizabeth A. Winzeler, Francisco-Javier Gamo, David A. Fidock, Delphine Baud, Michael W. Parker, Stephen Brand, Lawrence R. Dick, Michael D. W. Griffin, Alexandra E. Gould, Leann Tilley
Summary: The study identifies the Plasmodium falciparum proteasome as a potential antimalarial drug target and develops a series of potent inhibitors with high efficacy against malaria parasites and low likelihood of resistance. These findings offer insights for designing potent and selective antimalarial proteasome inhibitors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Stanley C. Xie, Riley D. Metcalfe, Elyse Dunn, Craig J. Morton, Shih-Chung Huang, Tanya Puhalovich, Yawei Du, Sergio Wittlin, Shuai Nie, Madeline R. Luth, Liting Ma, Mi-Sook Kim, Charisse Flerida A. Pasaje, Krittikorn Kumpornsin, Carlo Giannangelo, Fiona J. Houghton, Alisje Churchyard, Mufuliat T. Famodimu, Daniel C. Barry, David L. Gillett, Sumanta Dey, Clara C. Kosasih, William Newman, Jacquin C. Niles, Marcus C. S. Lee, Jake Baum, Sabine Ottilie, Elizabeth A. Winzeler, Darren J. Creek, Nicholas Williamson, Michael W. Parker, Stephen Brand, Steven P. Langston, Lawrence R. Dick, Michael D. W. Griffin, Alexandra E. Gould, Leann Tilley
Summary: This study identifies aminoacyl transfer RNA synthetases as potential drug targets and presents a novel compound that can inhibit these enzymes, effectively killing the malaria parasite.