Article
Biochemistry & Molecular Biology
Suk Woo Kang, James Antoney, David W. Lupton, Robert Speight, Colin Scott, Colin J. Jackson
Summary: The stereoselective reduction of alkenes conjugated to electron-withdrawing groups has been extensively studied for the commercial production of fine chemicals. The old yellow enzyme (OYE) family and a subset of flavin/deazaflavin oxidoreductases (FDOR) have been shown to exhibit complementary enantioselectivity. This study explores several enzymes of the FDOR-A subgroup and identifies two enzymes (MSMEG_2027 and MSMEG_2850) that can selectively reduce a wide range of compounds. Protein crystallography and computational docking provide mechanistic insights into the observed stereoselectivity. These findings highlight the potential of FDOR and OYE families in asymmetric ene-reduction.
Review
Chemistry, Inorganic & Nuclear
Lindsay A. Davis, Mercy A. Oyugi, Jamariya Howard, Juan Corrales, Alaa Aziz, Charlene Mandimutsira, Joisha Girme, Amina Agbonoga, Ghader Bashiri, Edward N. Baker, Kayunta Johnson-Winters
Summary: F420-dependent glucose-6-phosphate dehydrogenase (FGD1) plays a crucial role in various bacteria, and its catalytic mechanism and structural properties have been extensively studied, leading to the recent discovery and investigation of similar enzymes in other microorganisms.
INORGANICA CHIMICA ACTA
(2021)
Article
Chemistry, Medicinal
Yanlin Jian, He Eun Forbes, Fabian Hulpia, Martijn D. P. Risseeuw, Guy Caljon, Helene Munier-Lehmann, Helena I. M. Boshoff, Serge Van Calenbergh
Summary: The study found that the meta-nitro substituents play a crucial role in the antitubercular activity of the synthesized compounds, and the introduction of polar substituents can reduce binding to bovine serum albumin. The most potent compound showed moderate inhibitory activity against Mycobacterium tuberculosis, but also exhibited mutagenicity in mammalian cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Jamal El Bakali, Michal Blaszczyk, Joanna C. Evans, Jennifer A. Boland, William J. McCarthy, Imam Fathoni, Marcio V. B. Dias, Eachan O. Johnson, Anthony G. Coyne, Valerie Mizrahi, Tom L. Blundell, Chris Abell, Christina Spry
Summary: By performing a fragment screen, we identified three series of fragments that occupy distinct regions in the active site of MtbPPAT. Guided by X-ray crystal structures, we successfully linked weakly-binding fragments to produce an active site binder with Mtb activity, as demonstrated by CRISPR interference. This study represents a significant progress in validating MtbPPAT as a potential drug target and designing anti-TB drugs targeting MtbPPAT.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Alexandre Gouzy, Claire Healy, Katherine A. Black, Kyu Y. Rhee, Sabine Ehrt
Summary: In acidic pH conditions, Mycobacterium tuberculosis adapts its metabolism to preferentially assimilate lipids, like oleic acid, over carbohydrates. Lack of certain enzymes necessary for lipid assimilation can be lethal to M. tuberculosis under acidic conditions, highlighting the pathogen's ability to alter its carbon diet in response to pH stress.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Microbiology
Cara Adolph, Matthew B. McNeil, Gregory M. Cook
Summary: New drugs are urgently needed to combat tuberculosis. This study provides insight into the importance of succinate oxidation in Mycobacterium tuberculosis and the consequences of inhibiting this process. Additionally, the study shows that impaired succinate oxidation affects the activity of anti-tuberculosis drugs. These findings are valuable for the development of bioenergetic inhibitors.
Article
Biochemistry & Molecular Biology
Marta Alberti, Stefano Sainas, Erika Ronchi, Marco L. Lolli, Donatella Boschi, Menico Rizzi, Davide M. Ferraris, Riccardo Miggiano
Summary: Researchers have characterized the full-length MTB DHODH and discovered the first selective inhibitor. This study has significant implications for drug treatment of tuberculosis.
Article
Biochemical Research Methods
Kamil Kaminski, Jan Ludwiczak, Maciej Jasinski, Adriana Bukala, Rafal Madaj, Krzysztof Szczepaniak, Stanislaw Dunin-Horkawicz
Summary: Rossmann fold enzymes play important roles in biochemical pathways such as nucleotide and amino acid metabolism. This study used deep learning models based on the sequence and structural features of the beta alpha beta motif to predict the specificity of enzymes towards cofactors. The results showed highly accurate predictions, demonstrating the significance of this research for studying enzyme functions.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Multidisciplinary Sciences
Wassihun Wedajo Aragaw, Brendon M. Lee, Xuan Yang, Matthew D. Zimmerman, Martin Gengenbacher, Wai-Keung Chui, Colin J. Jackson, Thomas Dick
Summary: The tuberculosis drug TA-C is metabolized by mycobacterial oxidoreductases to produce a more potent DHFR inhibitor than the parent compound, explaining the discrepancy between enzymatic and whole-cell activity observed in previous studies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Suk Woo Kang, James Antoney, David W. Lupton, Robert Speight, Colin Scott, Colin J. Jackson
Summary: Asymmetric reduction by ene-reductases has been extensively studied, with the Old Yellow Enzyme (OYE) family being the most researched. However, the limited substrate range and stereocomplementary pairs of current ene-reductases necessitate the development of a complementary class. Flavin/deazaflavin oxidoreductases (FDORs) that use F-420 as a cofactor have gained attention due to their stereocomplementarity with OYEs. In this study, the activity of eight FDOR-B enzymes was investigated, comparing their specific activity, kinetic properties, and stereoselectivity with FDOR-A enzymes and OYE family.
Article
Chemistry, Medicinal
Joanna C. Evans, Dinakaran Murugesan, John M. Post, Vitor Mendes, Zhe Wang, Navid Nahiyaan, Sasha L. Lynch, Stephen Thompson, Simon R. Green, Peter C. Ray, Jeannine Hess, Christina Spry, Anthony G. Coyne, Chris Abell, Helena I. M. Boshoff, Paul G. Wyatt, Kyu Y. Rhee, Tom L. Blundell, Clifton E. I. I. I. I. I. I. Barry, Valerie Mizrahi
Summary: Coenzyme A (CoA) is an essential cofactor in all living cells, and the pathway to CoA biosynthesis is considered a potential source of novel tuberculosis drug targets. This study identified a small molecule inhibitor, compound 1f, that displays on-target activity against Mtb CoaBC, confirming the druggability of this target. Metabolomic profiling following exposure to compound 1f in wild-type Mtb H37Rv produced a signature consistent with perturbations in pantothenate and CoA biosynthesis.
ACS INFECTIOUS DISEASES
(2021)
Article
Multidisciplinary Sciences
Rudolf Markt, Mathias Wunderer, Eva Maria Prem, Mira Mutschlechner, Nina Lackner, Andreas Otto Wagner
Summary: The cofactor F420 plays a central role in the metabolism of many bacterial and archaeal taxa, particularly in methanogenesis. Variability in polyglutamate tail length can be used as a tool to distinguish different groups and pathways. The method described in the protocol successfully extracted and detected F420 from various microbial communities, providing information on expression levels and tail-length profiles.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Article
Biochemistry & Molecular Biology
Saif Khan, Mahvish Khan, Mohtashim Lohani, Saheem Ahmad, Subuhi Sherwani, Sundeep Bhagwath, Mohd Wajid A. Khan, Mohd Wahid, Farrukh Aqil, Shafiul Haque
Summary: This study investigated the unfolding of Mycobacterium Aspartate beta semialdehyde dehydrogenase (ASADH) using spectroscopic techniques and size exclusion chromatography. The unfolding of the apo ASADH was found to be non-cooperative, while the unfolding of the holoenzyme was cooperative. The presence of NADP/H stabilizes the tryptophan environment and the native NADP/H-bound enzyme. The folded holoenzyme was shown to be conformationally more stable compared to the apo state. These findings are important for the discovery of novel drugs targeting ASADH.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Microbiology
Christian Heryakusuma, Dwi Susanti, Hang Yu, Zhou Li, Endang Purwantini, Robert L. Hettich, Victoria J. Orphan, Biswarup Mukhopadhyay
Summary: Anaerobic methanotrophic archaea (ANME) oxidize methane in marine sediments through associations with sulfate-reducing bacteria. The study showed that FsrII from ANME-2c functions as F-420-dependent nitrite reductase (FNiR), revealing functional specialization within the Fsr protein family.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Microbiology
Romain Veyron-Churlet, Jean-Michel Saliou, Camille Locht
Summary: Deciphering protein-protein interactions through BioID technology in Mycobacterium smegmatis revealed the interconnectedness of HbhA with cholesterol degradation and heme/iron pathways. The study highlights the potential of in vivo techniques to study complex protein interactions in bacteria.
ENVIRONMENTAL MICROBIOLOGY
(2021)
Article
Materials Science, Paper & Wood
Yun Qian, Yuichiro Otsuka, Tomonori Sonoki, Biswarup Mukhopadhyay, Masaya Nakamura, Jody Jellison, Barry Goodell
Article
Microbiology
Anna A. Perevalova, Ilya V. Kublanov, Salima Kh. Bidzhieva, Biswarup Mukhopadhyay, Elizaveta A. Bonch-Osmolovskaya, Alexander V. Lebedinsky
INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY
(2016)
Article
Microbiology
Endang Purwantini, Lacy Daniels, Biswarup Mukhopadhyay
JOURNAL OF BACTERIOLOGY
(2016)
Article
Biochemistry & Molecular Biology
Dwi Susanti, Usha Loganathan, Biswarup Mukhopadhyay
JOURNAL OF BIOLOGICAL CHEMISTRY
(2016)
Article
Genetics & Heredity
Dwi Susanti, Eric F. Johnson, Alla Lapidus, James Han, T. B. K. Reddy, Manoj Pilay, Natalia N. Ivanova, Victor M. Markowitz, Tanja Woyke, Nikos C. Kyrpides, Biswarup Mukhopadhyay
STANDARDS IN GENOMIC SCIENCES
(2016)
Article
Microbiology
Mitchell T. Caudill, James A. Budnick, Lauren M. Sheehan, Christian R. Lehman, Endang Purwantini, Biswarup Mukhopadhyay, Clayton C. Caswell
Article
Infectious Diseases
Jayasimha Rao, Dwi Susanti, Johnathon C. Childress, Michael C. Mitkos, Joshua K. Brima, Anthony W. Baffoe-Bonnie, Samuel N. Pearce, Dale Grgurich, Maria Jose Fernandez-Cotarelo, Thomas M. Kerkering, Biswarup Mukhopadhyay
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2018)
Article
Plant Sciences
Monica Balsera, Estefania Uberegui, Dwi Susanti, Ruth A. Schmitz, Biswarup Mukhopadhyay, Peter Schuermann, Bob B. Buchanan
Article
Multidisciplinary Sciences
Dwi Susanti, Joshua H. Wong, William H. Vensel, Usha Loganathan, Rebecca DeSantis, Ruth A. Schmitz, Monica Balsera, Bob B. Buchanan, Biswarup Mukhopadhyay
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2014)
Review
Microbiology
Trudy Torto-Alalibo, Endang Purwantini, Jane Lomax, Joao C. Setubal, Biswarup Mukhopadhyay, Brett M. Tyler
FRONTIERS IN MICROBIOLOGY
(2014)
Article
Microbiology
Endang Purwantini, Trudy Torto-Alalibo, Jane Lomax, Joao C. Setubal, Brett M. Tyler, Biswarup Mukhopadhyay
FRONTIERS IN MICROBIOLOGY
(2014)
Article
Chemistry, Multidisciplinary
Dwi Susanti, Usha Loganathan, Austin Compton, Biswarup Mukhopadhyay
Article
Microbiology
Yusuf Sofyan Efendi, Dwi Susanti, Erman Tritama, Michelle Lueders Pasier, Gilang Nadia Niwan Putri, Sugeng Raharso, Iskandar, Pingkan Aditiawati, Ernawati Arifin Giri-Rachman, Biswarup Mukhopadhyay, Endang Purwantini
GENOME ANNOUNCEMENTS
(2017)
Article
Microbiology
Dwi Susanti, Eric F. Johnson, Alla Lapidus, James Han, T. B. K. Reddy, Supratim Mukherjee, Manoj Pillay, Anna A. Perevalova, Natalia N. Ivanova, Tanja Woyke, Nikos C. Kyrpides, Biswarup Mukhopadhyay
GENOME ANNOUNCEMENTS
(2017)
Proceedings Paper
Computer Science, Theory & Methods
Jayanta Kumar Das, Atrayee Majumder, Pabitra Pal Choudhury, Biswarup Mukhopadhyay
2016 IEEE 6TH INTERNATIONAL CONFERENCE ON ADVANCED COMPUTING (IACC)
(2016)