Article
Multidisciplinary Sciences
Hengjun Cui, Andreas U. Mueller, Marc Leibundgut, Jiawen Tian, Nenad Ban, Eilika Weber-Ban
Summary: This study presents crystal structures of Dop in different functional states, providing insights into the catalytic mechanism of this enzyme. Pupylation and depupylation are reversible protein modification processes mainly acting in members of Actinobacteria.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Mubarak A. Alamri, Sajjad Ahmad, Safar M. Alqahtani, Muhammad Irfan, Alhumaidi B. Alabbas, Muhammad Tahir Ul Qamar
Summary: Tuberculosis remains a major global public health concern. The development of new drugs is necessary due to the emergence of drug-resistant strains of Mycobacterium tuberculosis. In this study, comprehensive computational methods were used to identify compounds that bind to essential enzymes involved in biotin synthesis and ligation of M. tuberculosis. Two compounds were found to consistently bind to the enzymes with high affinity. These compounds could potentially be used in the design of effective anti-tuberculosis therapeutics by inhibiting bacterial growth through blocking biotin biosynthesis.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Jing Wang, Pupu Ge, Zehui Lei, Zhe Lu, Lihua Qiang, Qiyao Chai, Yong Zhang, Dongdong Zhao, Bingxi Li, Jiaqi Su, Ruchao Peng, Yu Pang, Yi Shi, Yu Zhang, George Fu Gao, Xiao-Bo Qiu, Cui Hua Liu
Summary: The study reveals that PknG acts as both a ubiquitin-activating enzyme and ligase, promoting the degradation of key components of the immune system and inhibiting NF-kappa B signaling, providing a potential target for tuberculosis treatment.
Article
Cell Biology
Sidi Zhang, Euki Yazaki, Hirokazu Sakamoto, Hayashi Yamamoto, Noboru Mizushima
Summary: The ATG ubiquitin-like conjugation systems, ATG12 and ATG8, play important roles in macroautophagy. This study constructs a transcriptome database and identifies ATG conjugation system components in 94 eukaryotic species. It finds that functional diversification of these systems is more common than previously thought.
Review
Biotechnology & Applied Microbiology
Jonathan Picker, Ziyang Lan, Srishtee Arora, Mykel Green, Mariah Hahn, Elizabeth Cosgriff-Hernandez, Magnus Hook
Summary: Collagens, as the major structural component in animal extracellular matrices, play crucial roles in cell-matrix interactions. The unique triple helical structure of collagens is enabled by Gly-X-Y repeats. Prokaryotic collagen-like proteins, which were discovered in the early 2000s, have similar structures to mammalian collagens and can be easily expressed in E. coli and genetically modified. This review article discusses the properties of mammalian collagen, compares mammalian collagen with prokaryotic collagen-like proteins, and reviews the applications of prokaryotic collagen-like proteins in studying collagen biology and developing new biomaterial platforms. Furthermore, it describes the application of the streptococcal collagen-like protein Scl2 in thromboresistant coating, scaffolds for bone regeneration, chronic wound dressing, and matrices for cartilage regeneration.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Guido Janssen, Susan Zhang, Remco Merkx, Christa Schiesswohl, Champak Chatterjee, K. Heran Darwin, Paul P. Geurink, Gerbrand J. van der Heden van Noort, Huib Ovaa
Summary: Tuberculosis is a global health problem caused by Mycobacterium tuberculosis infection. New drugs targeting Mtb are urgently needed due to the existence of drug resistant strains. The Pup proteasome system has been identified as a potential target for drug development, with inhibitors of Dop and PafA showing promising results in inhibiting Mtb activity.
Article
Biochemistry & Molecular Biology
Leena Hussein Bajrai, Aiah M. Khateb, Maha M. Alawi, Hashim R. Felemban, Anees A. Sindi, Vivek Dhar Dwivedi, Esam Ibraheem Azhar
Summary: This study demonstrates the potential of a diverse set of glycosylated flavonoids as inhibitors of Mtb CYP121. The findings provide a basis for further experimental validation and development of therapies for drug-resistant Mtb strains.
Article
Microbiology
Jan Madacki, Mickael Orgeur, Guillem Mas Fiol, Wafa Frigui, Laurence Ma, Roland Brosch
Summary: The study revealed that interstrain DNA transfer among tubercle bacilli is independent of a functional ESX-1 type VII secretion system, contrasting with the widely studied model organism Mycobacterium smegmatis. This finding provides new insights into the genetic events driving the pathoevolution of M. tuberculosis and challenges previous perceptions of HGT in mycobacteria, particularly for species lacking ESX-1 secretion systems.
Article
Cell Biology
Erez Zerbib, Shai Schlussel, Nir Hecht, Noy Bagdadi, Jerry Eichler, Eyal Gur
Summary: This study demonstrates that bacterial prokaryotic ubiquitin-like protein can escape proteasomal degradation and remain conjugated to the target, facilitating its recycling and re-conjugation to a new target. The lack of susceptibility to proteasome-mediated cleavage plays a mechanistic role in the biological system.
Article
Biochemistry & Molecular Biology
Sadhana Sundararajan, Keerthana Karunakaran, Rajiniraja Muniyan
Summary: The highly flexible nature of Mycobacterium tuberculosis (Mtb) is attributed to its tough cell wall and multiple gene interaction system, making it resistant to frontline TB drugs. In this study, in-silico structure based drug discovery was used to understand the interaction of compounds from an open source library (NPASS) with the target protein FabD. Three compounds with strong binding energies were identified and further evaluated for their interaction with FabD protein. The potential hit compounds could be considered for in-vitro evaluation against mutated FabD protein.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Biochemistry & Molecular Biology
Deepa Kumari, Jeffrey L. Brodsky
Summary: Protein quality control processes are crucial for cellular and organism health, particularly for polypeptides entering the endoplasmic reticulum (ER). ER-associated degradation (ERAD) is a multi-step pathway that targets inefficiently matured proteins for degradation, providing a mechanism to regulate protein levels and activities in the ER.
Article
Multidisciplinary Sciences
Matthias F. Block, Cyrille L. Delley, Lena M. L. Keller, Timo T. Stuehlinger, Eilika Weber-Ban
Summary: Pupylation is a post-translational modification found in Mycobacterium tuberculosis and other Actinobacteria, which involves the attachment of prokaryotic ubiquitin-like protein (Pup) to lysines on target proteins by the ligase PafA. Proteomic studies suggest that hundreds of potential pupylation targets are modified by PafA. This study shows that the availability of surface lysines alone is not sufficient for interaction between PafA and target proteins, and identifies the structural recognition motif involved in PafA's recognition of authentic substrates.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Tian Wang, Chuntong Li, Meijing Wang, Jiachen Zhang, Qingyun Zheng, Lujun Liang, Guochao Chu, Xiaolin Tian, Haiteng Deng, Wei He, Lei Liu, Jinghong Li
Summary: ISG15 protein tools are crucial for studying innate immunity and antiviral responses. This study discovered that the leader protease from foot-and-mouth disease virus can facilitate ligation reactions between ISG15 and synthetic compounds, resulting in the generation of necessary ISG15 protein tools.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Vivek Vinod, Anju Choorakottayil Pushkaran, Anil Kumar, Chethampadi Gopi Mohan, Raja Biswas
Summary: The study investigates the interaction mechanism of Mycobacterium tuberculosis GroEL2 protein with macrophage LOX-1 receptor. GroEL2 protein enhances the uptake of latex beads into macrophages through LOX-1 receptor, while LOX-1 inhibitor PIA decreases the uptake of GroEL2-coated latex beads. GroEL2 interacts with key ligand binding regions of LOX-1 receptor and PIA destabilizes the GroEL2-LOX-1 complex.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Article
Biochemistry & Molecular Biology
Shamba Gupta, Madhuri Bhagavathula, Vartika Sharma, Nishant Sharma, Nevadita Sharma, Ashis Biswas, Ainhoa Palacios, Vivian Salgueiro, Jose L. Lavin, Navneet Dogra, Padmini Salgame, Rafael Prados-Rosales, G. Marcela Rodriguez
Summary: In this study, the authors use a genetic approach to identify two proteins, IniA and IniC, that play a critical role in the formation of extracellular vesicles (EVs) in Mycobacterium tuberculosis (Mtb) in response to iron limitation and antibiotic exposure. They find that EV production allows intracellular Mtb to export bacterial components into the extracellular environment, which may modulate the immune response. These findings advance our understanding of mycobacterial EV biogenesis and function, and provide a potential target for therapeutic intervention.
Article
Multidisciplinary Sciences
Stephan Wilmes, Maximillian Hafer, Joni Vuorio, Julie A. Tucker, Hauke Winkelmann, Sara Loechte, Tess A. Stanly, Katiuska D. Pulgar Prieto, Chetan Poojari, Vivek Sharma, Christian P. Richter, Rainer Kurre, Stevan R. Hubbard, K. Christopher Garcia, Ignacio Moraga, Ilpo Vattulainen, Ian S. Hitchcock, Jacob Piehler
Editorial Material
Biochemistry & Molecular Biology
K. Heran Darwin
Summary: Good manners are important in both science and other areas, including the behavior of researchers on social media.
Editorial Material
Biochemistry & Molecular Biology
K. Heran Darwin
Article
Biochemistry & Molecular Biology
Shoshanna C. Kahne, K. Heran Darwin
Summary: Bacteria use proteolytic machines for protein quality control and response to environmental conditions, with ClpP proteases and bacterial proteasomes being common mechanisms, where activators play a key role. Understanding these mechanisms can lead to new approaches in designing targeted therapeutics.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
K. Heran Darwin
Summary: In academic research, there is no perfect recipe for balancing work and life. It is important for individuals to find their own optimal balance to derive fulfillment from both aspects.
Article
Chemistry, Medicinal
Hao Zhang, Hao-Chi Hsu, Shoshanna C. Kahne, Ryoma Hara, Wenhu Zhan, Xiuju Jiang, Kristin Burns-Huang, Tierra Ouellette, Toshihiro Imaeda, Rei Okamoto, Masanori Kawasaki, Mayako Michino, Tzu-Tshin Wong, Akinori Toita, Takafumi Yukawa, Francesca Moraca, Jeremie Vendome, Priya Saha, Kenjiro Sato, Kazuyoshi Aso, John Ginn, Peter T. Meinke, Michael Foley, Carl F. Nathan, K. Heran Darwin, Huilin Li, Gang Lin
Summary: Current treatment of tuberculosis (TB) typically lasts at least 6 months, with the latent Mycobacterium tuberculosis (Mtb) being tolerant to most anti-TB drugs. A key hypothesis is that drugs targeting the Mtb proteasome (Mtb20S) may shorten treatment time when used in combination with conventional drugs. A series of macrocyclic peptides, including macrocycle 6, have been developed that selectively target the Mtb20S and have the potential to be developed as anti-TB therapeutics.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Editorial Material
Biochemistry & Molecular Biology
K. Heran Darwin
Summary: Mycobacterium tuberculosis is a deadly pathogen with the ability to resist attacks from the immune system or drugs.
Editorial Material
Biochemistry & Molecular Biology
K. Heran Darwin
Summary: Principal Investigators do not have to avoid bench work; in fact, they are often the best and most experienced experimenters in the lab.
Editorial Material
Biochemistry & Molecular Biology
K. Heran Darwin
Summary: Research in life sciences is often wasteful. Can we reduce waste by improving our laboratories?
Editorial Material
Biochemistry & Molecular Biology
K. Heran Darwin
Summary: This article provides some advice on how to deal with, organise, and enjoy sharing science at meetings as COVID wanes and scientific conferences come back.
Editorial Material
Biochemistry & Molecular Biology
K. Heran Darwin
Editorial Material
Biochemistry & Molecular Biology
K. Heran Darwin, Bree Aldridge, Jessica Seeliger, Aimee Shen, Sarah Stanley
Article
Microbiology
Gina Limon, Nora M. Samhadaneh, Alejandro Pironti, K. Heran Darwin
Summary: M. tuberculosis is a leading cause of death and an effective vaccine is lacking. However, immunocompetent humans can control M. tuberculosis infections. This study shows that aldehydes can increase M. tuberculosis susceptibility to copper, suggesting a previously unappreciated antimicrobial defense.
Editorial Material
Biochemistry & Molecular Biology
K. Heran Darwin
Article
Biochemistry & Molecular Biology
Yanting Yin, Amanda Kovach, Hao-Chi Hsu, K. Heran Darwin, Huilin Li
Summary: The bacterial proteasome ATPase Mpa in Mycobacterium tuberculosis forms a gapped ring structure with highly flexible ATPase domains when in the presence of a degradation substrate and ATP, suggesting an intermediate state for engaging with proteasome CPs. The conformational changes in the linkers between domains play a crucial role in ATP hydrolysis-driven protein unfolding, highlighting a previously unappreciated function of the linker region. This study provides insights into the crucial process of how an ATPase interacts with a bacterial proteasome protease.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)