Article
Cell Biology
Jyoti Adlakha, Zhouping Hong, PeiQi Li, Karin M. Reinisch
Summary: VPS13 proteins act as bridges between organelles, facilitating directional and bulk lipid transport. They are anchored between membranes through interactions with receptors. The study reveals that Mcp1p and XK, two integral membrane proteins that interact with VPS13A, are scramblases.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jisub Hwang, Wanki Yoo, Seung Chul Shin, Kyeong Kyu Kim, Han-Woo Kim, Hackwon Do, Jun Hyuck Lee
Summary: This study elucidated the crystal structure and characterized the carboxylesterase EaEst2 derived from Exiguobacterium antarcticum. It belongs to the Family XIII group and shows a broad range of substrate specificities. EaEst2 has an optimal pH of 7.0 and loses activity at temperatures above 50°C. It also exhibits degradation activity towards BHET. The study demonstrates the industrial potential of EaEst2 as a biocatalyst through its structural and biochemical characterization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Ruchi Yadav, Valentine V. Courouble, Sanjay K. Dey, Jerry Joe E. K. Harrison, Jennifer Timm, Jesse B. Hopkins, Ryan L. Slack, Stefan G. Sarafianos, Francesc X. Ruiz, Patrick R. Griffin, Eddy Arnold
Summary: The study investigates the processing of the nsp7-11 polyprotein by Mpro enzyme in SARS-CoV-2. Integrative modeling techniques were used to determine the structure of the polyprotein, while proteolysis assays were used to assess the effect of inhibitors on Mpro processing. The findings provide insights into the essential process of polyprotein cleavage and its potential vulnerability to inhibition.
Article
Virology
Debajit Dey, Shishir Poudyal, Asma Rehman, S. Saif Hasan
Summary: Flaviviruses, such as yellow fever virus, are rapidly spreading arthropod-borne viruses causing severe symptoms, yet effective vaccines are limited. Insights into potential broad-spectrum vaccination targets for flaviviruses are currently lacking.
Article
Multidisciplinary Sciences
Rodolfo Ciuffa, Federico Uliana, Jonathan Mannion, Martin Mehnert, Tencho Tenev, Cathy Marulli, Ari Satanowski, Lena Maria Leone Keller, Pilar Natalia Rodilla Ramirez, Alessandro Ori, Matthias Gstaiger, Pascal Meier, Ruedi Aebersold
Summary: Protein-protein interactions (PPIs) are the main mode of proteome organization in cells. Traditional PPI networks lack contextual information. Generating context-dependent PPI networks is necessary for structural and systems-level modeling, but remains challenging. In this study, an experimental/computational strategy is described to achieve contextual modeling of PPIs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Brian E. Eckenroth, Joshua D. Bumgarner, Olivia Matsumoto-Elliott, Sheila S. David, Sylvie Doublie
Summary: Cellular DNA can be damaged from various sources and repaired using different systems depending on the context or cell cycle. DNA glycosylases are responsible for recognizing and removing oxidatively damaged bases. NEIL2 glycosylase, belonging to the Fpg/Nei family, can excise lesions in a wide range of DNA contexts, with a preference for oxidized cytosine products and abasic sites. The crystal structure of NEIL2 in complex with DNA duplex containing an abasic site analog has been determined.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Vega Miguel-Ruano, Ivanna Rivera, Jelena Rajkovic, Kamila Knapik, Ana Torrado, Jose Manuel Otero, Elisa Beneventi, Manuel Becerra, Mercedes Sanchez-Costa, Aurelio Hidalgo, Jose Berenguer, Maria-Isabel Gonzalez-Siso, Jacobo Cruces, L. Maria Rua, A. Juan Hermoso
Summary: The novel thermostable esterase EstD11 from a hot spring metagenomic library exhibits broad substrate specificity and belongs to the HSL family. Structural analysis and crystallographic experiments revealed the hot-spots in the active site and a unique Met zipper lining, providing insights into its enzymatic activity and stability.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biotechnology & Applied Microbiology
Pranay Jakkula, Bandigi Narsimulu, Insaf Ahmed Qureshi
Summary: 6-phosphogluconate dehydrogenase (6PGDH) of Leishmania donovani (Ld6PGDH) was cloned, purified, and characterized in this study, showing differences in structure and substrate affinity compared to other eukaryotes. The enzyme's activity can be inhibited more potently by specific drugs through competitive mode, and molecular docking studies revealed potential binding pockets for substrate and cofactor. Molecular dynamics simulations indicated the stability of Ld6PGDH complexes, laying a foundation for future research on this enzyme as a potential target against leishmaniasis.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Yuyuan Zheng, Lei Ding, Xianhui Meng, Meg Potter, Alison L. Kearney, Jie Zhang, Jie Sun, David E. James, Guang Yang, Chun Zhou
Summary: Research has revealed that SIN1 is a vital component of mTORC2 and can interact with Ras family small GTPases through its Ras-binding domain (RBD). The association between Ras and SIN1/mTORC2 can potentially impact both mTORC2 and Ras-ERK pathways. By determining the high-resolution structures of HRas/KRas-SIN1 RBD complexes, researchers have identified the detailed interaction interface. Mutations in critical interface residues disrupt the Ras-SIN1 interaction, and in SIN1 knockout cells, it has been shown that the Ras-SIN1 association promotes SGK1 activity but inhibits insulin-induced ERK activation. Comparison with other Ras-binding proteins and experimental assays suggest that the association between HRas and SIN1 RBD is weaker than HRas-Raf1 RBD but slightly stronger than HRas-PI3K RBD, potentially explaining the different outcomes of insulin or EGF stimulation. Additionally, a Ras dimerization interface critical for Ras oligomerization has been uncovered. These findings contribute to our understanding of the Ras-SIN1 association and the cross-talk between growth factor-stimulated pathways.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Yan Zhang, Xiaoyun Pang, Jian Li, Jiashu Xu, Victor W. Hsu, Fei Sun
Summary: By using cryoelectron microscopy, researchers have revealed the protein lattice formed by SNX1, which helps to understand how it functions in generating transport carriers. Comparing the structure of SNX1 with that of an endosomal coat complex formed by retromer coupled to a SNX provides insights into the molecular organization of SNX and the intermediary stages of assembly leading to the formation of the complex on the membrane.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Sofia Lemak, M. Anca Serbanescu, Anna N. Khusnutdinova, Milosz Ruszkowski, Natalia Beloglazova, Xiaohui Xu, Greg Brown, Hong Cui, Kemin Tan, Andrzej Joachimiak, Dennis G. Cvitkovitch, Alexei Savchenko, Alexander F. Yakunin
Summary: In this study, the crystal structure of SmuCas5c was determined, revealing its role in processing CRISPR RNA transcripts and its metal-independent ribonuclease activity. The analysis also showed significant sequence variation tolerance of SmuCas5c during substrate RNA cleavage.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Xiaoyun Yang, Jiaxu Wang, Simin Li, Xiaobing Li, Jingjing Gong, Zhenzhen Yan, Huan Zhou, Chen Wu, Xiuhua Liu
Summary: Nucleic acid ADP-ribosylation is a newly discovered modification found in various organisms. TRPT1 possesses ADP-ribosyltransferase activity and can modify nucleic acids. In this study, crystal structures of TRPT1 from different species were determined, revealing the mechanism of NAD(+) and nucleic acid substrate binding. The results also showed that TRPT1s use different residues for catalytic activity and nucleic acid binding. Cellular assays demonstrated that mammalian TRPT1 promotes cell survival and proliferation. Overall, this study provides insights into the molecular mechanism of TRPT1 in nucleic acid ADP-ribosylation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Ruth A. Pumroy, Anna D. Protopopova, Tabea C. Fricke, Iris U. Lange, Ferdinand M. Haug, Phuong T. Nguyen, Pamela N. Gallo, Barbara B. Sousa, Goncalo J. L. Bernardes, Vladimir Yarov-Yarovoy, Andreas Leffler, Vera Y. Moiseenkova-Bell
Summary: The study identifies a binding site for the activator 2-APB in TRPV2 and confirms the role of His521 and Arg539 in the activation process. Additionally, it shows that the combination of 2-APB and cannabidiol has a synergetic effect on TRPV2 activation.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Anica Dadwal, Vishal Singh, Shilpa Sharma, Amaresh Kumar Sahoo, Tulasi Satyanarayana
Summary: This study analyzed the structure and thermostability of the cellulase CBHII from Mycoeliophthora thermophila using in-silico approaches. It found that the enzyme has a high affinity for cellotetraose and exhibits tolerance to elevated temperatures.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Biochemistry & Molecular Biology
Asat Baischew, Sarah Engel, Thomas M. M. Geiger, Martha C. C. Taubert, Felix Hausch
Summary: FKBP51 is a high-molecular-weight immunophilin that is considered an important drug target for stress-related disorders, chronic pain, and obesity. It is involved in multiple molecular pathways, but its best characterized role is as a co-chaperone of Hsp90 in the steroid hormone receptor maturation cycle. However, the regulatory mechanism and structural basis of SHRs by FKBP51 and its homolog FKBP52 is still unknown. In this review, we discuss recent advances in the understanding of FKBPs as regulators in the Hsp90 machinery, providing important insights into the roles of FKBP51 and FKBP52 in SHR regulation.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Article
Nutrition & Dietetics
Padma Maruvada, Johanna W. Lampe, David S. Wishart, Dinesh Barupal, Deirdra N. Chester, Dylan Dodd, Yannick Djoumbou-Feunang, Pieter C. Dorrestein, Lars O. Dragsted, John Draper, Linda C. Duffy, Johanna T. Dwyer, Nancy J. Emenaker, Oliver Fiehn, Robert E. Gerszten, Frank B. Hu, Robert W. Karp, David M. Klurfeld, Maren R. Laughlin, A. Roger Little, Christopher J. Lynch, Steven C. Moore, Holly L. Nicastro, Diane M. O'Brien, Jose M. Ordovas, Stavroula K. Osganian, Mary Playdon, Ross Prentice, Daniel Raftery, Nichole Reisdorph, Helen M. Roche, Sharon A. Ross, Shengmin Sang, Augustin Scalbert, Pothur R. Srinivas, Steven H. Zeisel
ADVANCES IN NUTRITION
(2020)
Article
Multidisciplinary Sciences
Shan Sun, Lingjie Luo, Wenhua Liang, Qian Yin, Jing Guo, Anthony M. Rush, Zhibao Lv, Qiming Liang, Michael A. Fischbach, Justin L. Sonnenburg, Dylan Dodd, Mark M. Davis, Feng Wang
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Editorial Material
Engineering, Biomedical
John Jarman, Dylan Dodd
NATURE BIOMEDICAL ENGINEERING
(2020)
Article
Multidisciplinary Sciences
Shuo Han, Will Van Treuren, Curt R. Fischer, Bryan D. Merrill, Brian C. DeFelice, Juan M. Sanchez, Steven K. Higginbottom, Leah Guthrie, Lalla A. Fall, Dylan Dodd, Michael A. Fischbach, Justin L. Sonnenburg
Summary: Research has shown that gut microorganisms can influence host physiology, and using mass spectrometry technology can accelerate the identification of microbial metabolites, thereby enabling in-depth study of the relationship between microorganisms and hosts.
Article
Biochemistry & Molecular Biology
Victoria Pascal Andreu, Jorge Roel-Touris, Dylan Dodd, Michael A. Fischbach, Marnix H. Medema
Summary: The gutSMASH web server, developed to analyze the metabolic potential of gut microbiomes, predicts known and novel pathways by predicting gene clusters. Users can easily upload files for analysis and obtain detailed results.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Microbiology
Yuanyuan Liu, Haoqing Chen, William Van Treuren, Bi-Huei Hou, Steven K. Higginbottom, Dylan Dodd
Summary: The gut bacterium Clostridium sporogenes uses a process called the Stickland reaction to obtain energy and produces circulating metabolites in the host. Reductive metabolism is found to be linked to ATP formation and the Rnf complex plays a key role in energy transduction.
NATURE MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Elisabeth Serger, Lucia Luengo-Gutierrez, Jessica S. Chadwick, Guiping Kong, Luming Zhou, Greg Crawford, Matt C. Danzi, Antonis Myridakis, Alexander Brandis, Adesola Temitope Bello, Franziska Muller, Alexandros Sanchez-Vassopoulos, Francesco De Virgiliis, Phoebe Liddell, Marc Emmanuel Dumas, Jessica Strid, Sridhar Mani, Dylan Dodd, Simone Di Giovanni
Summary: Intermittent fasting promotes axonal regeneration and accelerates recovery of sensory function after sciatic nerve injury in mice, relying on the gram-positive gut microbiome and the increase in the gut bacteria-derived metabolite indole-3-propionic acid (IPA). This effect is mediated by neutrophil chemotaxis.
Article
Physiology
Hong Xiang, Haoqing Chen, Yuanyuan Liu, Dylan Dodd, Alan C. Pao
Summary: This study found that ob/ob mice excrete more urine oxalate compared to wild type mice due to their obesity. Treatment with antibiotics, leptin, or pioglitazone did not change urine oxalate excretion in ob/ob mice. The increased urine oxalate excretion in ob/ob mice is likely caused by hyperphagia. Standardization of urine oxalate measurement is needed for accurate comparisons between different mouse strains or models.
PHYSIOLOGICAL REPORTS
(2022)
Article
Medicine, Research & Experimental
Dylan Dodd, Isaac Cann
Summary: The human gut microbiome plays a crucial role in drug metabolism by producing small molecules and modifying drugs directly. Recent studies have uncovered the extensive and potential impact of microbial drug metabolism, providing the possibility to predict an individual's capacity for drug metabolism.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)
Article
Multidisciplinary Sciences
Kali M. Pruss, Haoqing Chen, Yuanyuan Liu, William Van Treuren, Steven K. Higginbottom, John B. Jarman, Curt R. Fischer, Justin Mak, Beverly Wong, Tina M. Cowan, Michael A. Fischbach, Justin L. Sonnenburg, Dylan Dodd
Summary: The human gut microbiota produces various small molecules that have significant effects on host physiology. However, little is known about the origin and fate of these metabolites. In this study, researchers identified a co-metabolic pathway between the host and gut bacteria for the production of hippuric acid, a major organic acid in mammalian urine. They found that gut bacteria convert phenylalanine to phenylpropionic acid, which is then re-oxidized by the host using medium-chain acyl-CoA dehydrogenase (MCAD). Through experiments with germ-free mice, the researchers also identified other microbial metabolites processed by MCAD in the host circulation. This study reveals a novel mechanism by which mammals metabolize microbiota-derived metabolites and highlights the importance of host-microbe co-metabolism in the generation and processing of these metabolites.
NATURE COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Victoria Pascal Andreu, Hannah E. E. Augustijn, Lianmin Chen, Alexandra Zhernakova, Jingyuan Fu, Michael A. A. Fischbach, Dylan Dodd, Marnix H. H. Medema
Summary: Profile hidden Markov models are used to identify taxon-specific primary metabolic pathways. The gut microbiota produce various small molecules that modulate host physiology. The gutSMASH algorithm is introduced to identify primary metabolic gene clusters in high-quality microbial genomes, revealing marked differences in pathway distribution among phyla and indicating a characteristic metabolic niche for each taxon. The study also highlights the crucial role of pathway-specific gene regulation and metabolite flux in microbiome-derived metabolites.
NATURE BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Cecilia Noecker, Juan Sanchez, Jordan E. Bisanz, Veronica Escalante, Margaret Alexander, Kai Trepka, Almut Heinken, Yuanyuan Liu, Dylan Dodd, Ines Thiele, Brian C. DeFelice, Peter J. Turnbaugh
Summary: Human gut bacterium Eggerthella lenta performs diverse chemical transformations and uses acetate as a key carbon source while catabolizing arginine to generate ATP. The metabolic network of E. lenta was comprehensively studied through various resources, including defined culture media, metabolomics profiles, and a curated genome-scale metabolic reconstruction. The findings demonstrate a distinctive metabolic niche filled by E. lenta in the gut ecosystem, providing valuable resources for further research on this prevalent gut bacterium.
Article
Biochemistry & Molecular Biology
Yuanyuan Liu, J. Bryce Jarman, Yen S. Low, Hannah E. Augustijn, Steven Huang, Haoqing Chen, Mary E. DeFeo, Kazuma Sekiba, Bi-Huei Hou, Xiandong Meng, Allison M. Weakley, Ashley V. Cabrera, Zhiwei Zhou, Gilles van Wezel, Marnix H. Medema, Calyani Ganesan, Alan C. Pao, Saurabh Gombar, Dylan Dodd
Summary: Approximately 15% of US adults have high levels of circulating uric acid, which is causally related to gout. In this study, a gene cluster in gut bacteria was found to encode a pathway for uric acid degradation. Gut bacteria metabolize uric acid to xanthine or short chain fatty acids, revealing their role in uric acid excretion. Manipulating the gut microbiota could be a potential therapeutic approach for hyperuricemia.
Article
Endocrinology & Metabolism
Kali M. Pruss, Fatima Enam, Eric Battaglioli, Mary DeFeo, Oscar R. Diaz, Steven K. Higginbottom, Curt R. Fischer, Andrew J. Hryckowian, William Van Treuren, Dylan Dodd, Purna Kashyap, Justin L. Sonnenburg
Summary: The pathogen Clostridioides difficile (Cd) can colonize the gut even without causing any symptoms of the disease. The prevalence of asymptomatic colonization by toxigenic Cd in healthy populations is high. In this study, researchers analyzed the gut microbiome of mice resistant to Cd infection and inflammation and found increased expression of arginine and ornithine metabolic pathways. They also identified a specific operon consistently upregulated in non-toxigenic Cd strains. Through metabolomics and genetic analysis, the researchers demonstrated that both diet- and host-derived sources of ornithine provide a competitive advantage to Cd, suggesting a mechanism for Cd persistence in a non-inflammatory, healthy gut.
Meeting Abstract
Agriculture, Dairy & Animal Science
Dylan Dodd
JOURNAL OF ANIMAL SCIENCE
(2020)