Article
Biochemistry & Molecular Biology
Milena Maya-Hoyos, Dulce Mata-Espinosa, Manuel O. Lopez-Torres, Blanca Tovar-Vazquez, Jorge Barrios-Payan, Juan C. Leon-Contreras, Marisol Ocampo, Rogelio Hernandez-Pando, Carlos Y. Soto
Summary: Identification and targeting of CtpF as a potential attenuation target for Mycobacterium tuberculosis (Mtb) has shown reduced proliferation and virulence in mouse models, while maintaining immunogenicity. Differential expression levels of ctpF in latent and progressive TB mouse models suggest its involvement in Mtb persistence. Possible complementary mechanisms for Ca2+ transport deficiencies mediated by P-type ATPases are also indicated.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Henry A. Varon, Paola Santos, Fabian Lopez-Vallejo, Carlos Y. Soto
Summary: In this study, a potential anti-Mtb compound, ZINC04030361, was identified through molecular dynamics simulations and pharmacophore-based virtual screening. In vitro assays further confirmed its activity against CtpF and its potential as a novel anti-tuberculosis drug.
BIOORGANIC CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Anthony D. Rish, Zhangfei Shen, Zhenhang Chen, Nan Zhang, Qingfei Zheng, Tian-Min Fu
Summary: This study reports two cryo-EM structures of RuvB, revealing the mechanism of HJ branch migration. RuvB assembles into a spiral staircase, ring-like hexamer, enveloping double-stranded DNA. The asymmetric assembly of RuvB explains the 6:4 stoichiometry of the RuvB/RuvA complex in coordinating HJ migration in bacteria. These findings provide a mechanistic understanding of HJ branch migration facilitated by RuvB, which may be universally shared by prokaryotic and eukaryotic organisms.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Paige M. E. Hawkins, David M. Hoi, Chen-Yi Cheung, Trixie Wang, Diana Quan, Vishnu Mini Sasi, Dennis Y. Liu, Roger G. Linington, Colin J. Jackson, Stefan H. Oehlers, Gregory M. Cook, Warwick J. Britton, Tim Clausen, Richard J. Payne
Summary: Lead analogues of Ohmyungsamycin A and ecumicin were synthesized using solid-phase synthesis and macrolactamization strategy, and showed potent activity against Mtb. These analogues were found to inhibit protein degradation and enhance ATPase activity, and exhibited rapid bactericidal killing activity against Mtb in vitro and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biology
Gabrielle Taylor, Hengjun Cui, Julia Leodolter, Christoph Giese, Eilika Weber-Ban
Summary: This study reveals that the structure similar to ClpC1, ClpC2, can bind to the antitubercular compound CymA. CymA counteracts the toxicity of ClpC1 by binding to ClpC2. Deletion of clpC2 in Mycobacterium smegmatis increases sensitivity to CymA.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Gabrielle Taylor, Yannick Frommherz, Panagiotis Katikaridis, Dominik Layer, Irmgard Sinning, Marta Carroni, Eilika Weber-Ban, Axel Mogk
Summary: This study investigates the control of ClpC1 activity and how this control is disrupted by the antibacterial drug CymA. It was found that ClpC1 exists in various activity states and CymA can enhance ClpC1 activity and degradation activity towards substrates. The resting state of ClpC1 and the CymA-induced assembly state both rely on interactions between the middle domains of ClpC1. Furthermore, overexpression of this assembly state is toxic to other bacteria.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Gang Zhang, Shan Li, Kai-Wen Cheng, Tsui-Fen Chou
Summary: AAA ATPases, essential enzymes found in all organisms, are involved in various cellular activities. Researchers have identified and developed small-molecule inhibitors against these enzymes. Structural information suggests further development of specific AAA ATPase inhibitors in the future.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Dina Aweida, Shenhav Cohen
Summary: Protein degradation is essential for cellular integrity, with autophagy and the UPS being the main systems responsible for protein breakdown. Recent studies show that even complex protein structures can be efficiently degraded in vivo, with AAA-ATPases playing a crucial role in the disassembly process.
Review
Immunology
Cheldon Ann Alcantara, Ira Glassman, Kevin H. Nguyen, Arpitha Parthasarathy, Vishwanath Venketaraman
Summary: Mycobacterium tuberculosis (M. tb) remains a major cause of death in developing countries. The BCG vaccine is widely used in developing countries but its efficacy is still uncertain. Neutrophils play a crucial role in the immune response against M. tb, promoting clearance of the bacteria and regulating the inflammatory response. This review highlights the role of neutrophils during M. tb infection and emphasizes the need for more research on effective vaccination.
Article
Biochemistry & Molecular Biology
Katharina Weinhaupl, Marcos Gragera, M. Teresa Bueno-Carrasco, Rocio Arranz, Olga Krandor, Tatos Akopian, Raquel Soares, Eric Rubin, Jan Felix, Hugo Fraga
Summary: The unfoldase ClpC1 is an important drug target against tuberculosis, and its mechanism of action remains largely unknown. Using cryo-EM, we determined the structure of ClpC1 in different states and revealed the mechanism of ecumicin.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Immunology
Mariana Herrera, Yoav Keynan, Lucelly Lopez, Diana Marin, Lazaro Velez, Paul J. McLaren, Zulma Vanessa Rueda
Summary: We studied the immune changes in newly acquired tuberculosis infection in a population deprived of liberty in Colombian prisons. We found differences in immune levels between individuals with new tuberculosis infection and those incarcerated for short and long periods of time. Certain cytokines/chemokines were associated with new tuberculosis infection and tuberculosis disease.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Stephanie Fischinger, Deniz Cizmeci, Sally Shin, Leela Davies, Patricia S. Grace, Aida Sivro, Nonhlanhla Yende-Zuma, Hendrik Streeck, Sarah M. Fortune, Douglas A. Lauffenburger, Kogieleum Naidoo, Galit Alter
Summary: South Africa has the highest prevalence of HIV and tuberculosis co-infection globally, with HIV infected individuals having a greater likelihood of developing recurrent TB. This study investigated the humoral response in HIV co-infected individuals with and without recurrent TB, finding differences in antibody profiles, particularly decreased Mtb-antigen specific IgG3 titers in individuals with recurrent TB. These findings suggest a potential role for Mtb-specific IgG3 responses as biomarkers or mediators of protective immunity against Mtb recurrence.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemical Research Methods
Paula J. Gomez-Gonzalez, Susana Campino, Jody E. Phelan, Taane G. Clark
Summary: This study compared the genome sequencing of clinical isolates of Mycobacterium tuberculosis using Oxford Nanopore Technologies (ONT) sequencing and Illumina HiSeq sequencing. The analysis showed that ONT sequencing is robust for detecting single nucleotide polymorphisms and provides improved coverage in repetitive regions. It also demonstrated high concordance in variants associated with drug resistance. ONT sequencing is a promising tool for tuberculosis genomic investigations and can inform clinical and surveillance decision-making to reduce the disease burden.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Camilla Henriksen, Kristoffer T. Baek, Katarzyna Wacnik, Clement Gallay, Jan-Willem Veening, Simon J. Foster, Dorte Frees
Summary: This study provides genetic evidence for the role of ClpX unfoldase activity in coordinating bacterial cell division. The study shows that a Staphylococcus aureus clpX mutant with a spontaneously acquired G325V substitution in the essential FtsA protein's ATP-binding domain can rescue the growth defect. The results also suggest that ClpX promotes septum synthesis by antagonizing FtsA interactions.
MOLECULAR MICROBIOLOGY
(2023)
Article
Immunology
Shuping Li, Xiaohua Wang, Yuming Zhao, Juan Yang, Tianjiao Cui, Zhizhuang Joe Zhao, Yun Chen, Zhihua Zheng
Summary: The PTPN22-C1858T polymorphism is not significantly associated with higher susceptibility to M. tuberculosis infection in Caucasians and Asians, but is relevant to increased susceptibility to M. leprae infection. Further well-designed studies with sufficient populations are required to verify these conclusions.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Virology
Varada Anirudhan, Hyun Lee, Han Cheng, Laura Cooper, Lijun Rong
Summary: The review provides information on potential treatment strategies for COVID-19 that target the essential proteins of the virus, specifically 3CL(pro) and PLpro, which are key in inhibiting viral replication and may offer insights from previous experience with SARS-CoV.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Article
Chemistry, Medicinal
Zhengnan Shen, Kiira Ratia, Laura Cooper, Deyu Kong, Hyun Lee, Youngjin Kwon, Yangfeng Li, Saad Alqarni, Fei Huang, Oleksii Dubrovskyi, Lijun Rong, Gregory R. J. Thatcher, Rui Xiong
Summary: Researchers have discovered a new antiviral drug that targets the SARS-CoV-2 papain-like protease (PLpro) to inhibit viral replication and improve antiviral potency in human cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Youjin Lee, Neagawooridwimeu Kim, Pia Werlinger, Dong-A Suh, Hanki Lee, Joo-Hyung Cho, Jinhua Cheng
Summary: This study investigated the effect of Lactobacillus brevis MJM60390 on hyperuricemia induced by a high-purine diet and potassium oxonate in a mouse model. The results showed that supplementation with L. brevis MJM60390 reduced serum uric acid levels, inhibited xanthine oxidase activity, and reversed kidney damage. Additionally, the supplementation enhanced the relative abundance of beneficial bacteria producing butyrate.
JOURNAL OF MEDICINAL FOOD
(2022)
Article
Pharmacology & Pharmacy
Subodh Kumar Samrat, Jimin Xu, Xuping Xie, Eleonora Gianti, Haiying Chen, Jing Zou, Jason G. Pattis, Khaled Elokely, Hyun Lee, Zhong Li, Michael L. Klein, Pei-Yong Shi, Jia Zhou, Hongmin Li
Summary: In this study, researchers screened a drug library and identified JMX0286, JMX0301, and JMX0941 as potent allosteric inhibitors against SARS-CoV-2 3CLpro. They demonstrated the antiviral activity of these compounds through cell-based assays and characterized their mechanisms of action and binding sites.
ANTIVIRAL RESEARCH
(2022)
Article
Hematology
Maaike Van Trimpont, Amanda M. Schalk, Yanti De Visser, Hien Anh Nguyen, Lindy Reunes, Katrien Vandemeulebroecke, Evelien Peeters, Ying Su, Hyun Lee, Philip L. Lorenzi, Wai-Kin Chan, Veerle Mondelaers, Barbara De Moerloose, Tim Lammens, Steven Goossens, Pieter Van Vlierberghe, Arnon Lavie
Summary: Asparagine is crucial for the growth and survival of ALL cells, which are dependent on extracellular asparagine. Current L-asparaginases, while effective, have toxic side effects due to their co-activity with L-glutaminase. A new variant, ErA-TM, with decreased L-glutaminase co-activity and maintained L-asparaginase activity, has been developed. Fusion with an albumin binding domain (ABD) significantly increases its in vivo persistence. ABD-ErA-TM shows comparable antileukemic efficacy to pegylated-asparaginase but with fewer co-glutaminase-related side effects.
Article
Cell Biology
Min Soo Kim, Won Sung Lee, Hanki Lee, Wook Jin
Summary: This study uncovers the physiological role of TrkC as a key regulator of EWSR1-FLI1 in Ewing sarcoma, which has important implications for the survival and metastasis of ES cells. TrkC inhibits the degradation of EWSR1-FLI1, promoting ES cell metastasis and suppressing the tumor-suppressing activity of TGF-beta.
CELL DEATH & DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Hyun Lee, Lucas Ibrahimi, Dimitri T. Azar, Kyu-Yeon Han
Summary: MT1-MMP is a protease enzyme that regulates cellular activities, especially cell migration. It interacts with various molecules and can not only change the extracellular environment but also regulate cell signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jinhong Ren, Tasneem M. Vaid, Hyun Lee, Isabel Ojeda, Michael E. Johnson
Summary: This study investigates HCV NS3/4A inhibitors for the treatment of Hepatitis C infection. Molecular docking, molecular dynamics simulations, and MM/PBSA binding free energy calculations were used to explore inhibitor interactions with HCV NS3/4A. The quantitative assessments of binding free energies correlate well with the experimental results. Binding free energy decomposition analyses elucidate the different contributions of sidechains in binding different inhibitors, which was further confirmed by computational alanine scanning mutagenesis. The study provides valuable insights for future antiviral drug design.
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2022)
Article
Plant Sciences
So Young Lee, Gauri S. Shetye, So-Ri Son, Hyun Lee, Larry L. Klein, Jeffrey K. Yoshihara, Rui Ma, Scott G. Franzblau, Sanghyun Cho, Dae Sik Jang
Summary: This study identified several compounds from the fruits of Amomun tsao-ko that showed potential as anti-tuberculosis agents. These compounds exhibited significant antimicrobial activity against Mycobacterium tuberculosis, with tsaokol A being the most active and selective for treating tuberculosis.
Article
Critical Care Medicine
Hyung-Geun Moon, Seung-jae Kim, Ki-Hyun Kim, Young-Mee Kim, Jalees Rehman, Hyun Lee, Yi-Chien Wu, Steve Seung-Young Lee, John W. Christman, Steven J. Ackerman, Minhyung Kim, Sungyoung You, Gye Young Park
Summary: This study aims to investigate the cellular mechanism of tissue-resident macrophages involved in the resolution process of eosinophilic lung inflammation. Using mass cytometry, single-cell RNA sequencing, and biophysical and immunological analyses, it was found that the CCL26-CX3CR1 pathway plays a crucial role in resolving eosinophilic allergic lung inflammation.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Kiira M. Ratia, Zhengnan Shen, Jesse Gordon-Blake, Hyun Lee, Megan S. Laham, Isabella S. Krider, Nicholas Christie, Martha Ackerman-Berrier, Christopher Penton, Natalie G. Knowles, Soumya Reddy Musku, Jiqiang Fu, Ganga Reddy Velma, Rui Xiong, Gregory R. J. Thatcher
Summary: In aging and disease, NAD+ is depleted by catabolism to NAM. NAD+ supplementation is being pursued for human health benefits. Activation of NAMPT, the rate-limiting step in NAD+ biosynthesis, can increase NAM salvage. N-PAMs were discovered as novel NAMPT activators, with a mechanism of action involving the regulation of NAMPT turnover through the rear channel.
Article
Biochemistry & Molecular Biology
Hyun Lee, Isoo Youn, Robel Demissie, Tasneem M. Vaid, Chun-Tao Che, Dimitri T. Azar, Kyu-Yeon Han
Summary: Matrix metalloproteinases (MMPs) play important roles in physiological and pathological processes. In this study, a fluorescence-based enzymatic assay and surface plasmon resonance were used to identify MMP-14 inhibitors. Clioquinol and chloroxine, both containing a quinoline structure, showed selective inhibitory activity against MMP-14.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Tasneem M. Vaid, Robel Demissie, Youngjin Kwon, Thao Tran, Hyung-Geun Moon, Jose A. Villegas, Gye Young Park, Michael E. Johnson, Hyun Lee
Summary: This article applied a fragment-lead combination approach to identify small fragments that synergistically act with the CSF1R inhibitor GW2580. Several fragments were found to enhance the inhibitory activity of GW2580, and computational studies guided the design of potential next-generation compounds. The inhalability of the proposed compounds was predicted using quantitative structure-property relationships modeling. This work provides new insights into inhalable small molecule therapeutics for asthma.
Article
Allergy
Hyung-Geun Moon, Jacob D. Eccles, Seung-jae Kim, Ki-Hyun Kim, Young-Mee Kim, Jalees Rehman, Hyun Lee, Pinal Kanabar, John W. Christman, Steven J. Ackerman, Christian Ascoli, Homan Kang, Hak Soo Choi, Minhyung Kim, Sungyong You, Gye Young Park
Summary: C1q is selectively enriched in the CSF1R+cDC2 subset among conventional DCs, and it plays a critical role in allergen sensing and allergic lung inflammation. The C1q receptor CD91 (LRP1) is required for lung CSF1R+cDC2s to recognize the C1q-allergen complex and induce allergic lung inflammation.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Isoo Youn, Kyu-Yeon Han, Aleksandra Gurgul, Zhenlong Wu, Hyun Lee, Chun-Tao Che
Summary: Six undescribed compounds were isolated from the stem bark of Entandrophragma angolense, and their structures were determined. Some of these compounds showed anti-inflammatory effects in in vitro experiments.