Article
Biochemistry & Molecular Biology
Daniel Krochmal, Yaming Shao, Nan-Sheng Li, Saurja DasGupta, Sandip A. Shelke, Deepak Koirala, Joseph A. Piccirilli
Summary: Ribozymes that react with small-molecule probes have important applications in transcriptomics and chemical biology. This study focuses on a self-alkylating ribozyme and reports its crystal structures, showing a hook-shaped conformation.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Che-Hong Chen, Benjamin R. Kraemer, Lucia Lee, Daria Mochly-Rosen
Summary: Human ALDH is a multigene family with 19 functional members involved in detoxification and biotransformation. Genetic mutations can lead to toxic aldehyde accumulation and human pathologies. The physiological functions and substrate specificity of many ALDH genes are still unknown.
Editorial Material
Biochemistry & Molecular Biology
Jolanta Floryszak-Wieczorek, Ewa Sobieszczuk-Nowicka, Magdalena Arasimowicz-Jelonek
Summary: Nitroxyl (HNO), a one-electron reduced and protonated congener of nitric oxide (NO), has been recently discovered in Arabidopsis thaliana. Due to its distinct chemical properties, further studies are needed to determine the impacts of HNO on physiological processes.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Alexander Hanzl, Eleonora Barone, Sophie Bauer, Hong Yue, Radoslaw P. Nowak, Elisa Hahn, Eugenia V. Pankevich, Anna Koren, Stefan Kubicek, Eric S. Fischer, Georg E. Winter
Summary: Targeted protein degradation (TPD) is a new pharmacology approach that induces proximity between a protein of interest (POI) and an E3 ubiquitin ligase using small-molecule degraders. However, only a small percentage of E3s can be co-opted with degraders due to a lack of discovery approaches. This study focuses on NEDD8 conjugation and develops a scalable assay to identify compounds that alter the interactome of a specific E3 ligase.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Alexander Hanzl, Eleonora Barone, Sophie Bauer, Hong Yue, Radoslaw P. Nowak, Elisa Hahn, Eugenia V. Pankevich, Anna Koren, Stefan Kubicek, Eric S. Fischer, Georg E. Winter
Summary: Targeted protein degradation (TPD) is a new pharmacology that uses small-molecule degraders to induce proximity between a protein of interest (POI) and an E3 ubiquitin ligase. Only a small percentage of E3s can be co-opted with degraders due to a lack of discovery approaches. In this study, the focus is on dynamic NEDD8 conjugation, which enables the identification of compounds that alter the interactome of a specific E3 ligase. This strategy allows for scalable identification of degraders specific to a ligase of interest.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Agriculture, Multidisciplinary
Xiao Li, Jing-Nan Ren, Gang Fan, Lu-Lu Zhang, Si-Yi Pan
Summary: In this study, the enzyme involved in the (+)-valencene bioconversion by Y. lipolytica was isolated, purified, and identified. It was found to be aldehyde dehydrogenase (ALDH) with the highest activity at pH 6.0 and temperature of 30 degrees C. ALDH activity was stimulated by ferrous ions and inhibited by barium, calcium, and magnesium ions. This study provides a theoretical basis and reference for the biological synthesis of citrus flavor (+)-nootkatone.
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
(2023)
Article
Multidisciplinary Sciences
Shabareesh Pidathala, Aditya Kumar Mallela, Deepthi Joseph, Aravind Penmatsa
Summary: The researchers used the Drosophila melanogaster dopamine transporter as a surrogate to study the structure and function of norepinephrine, revealing potential paradigms for designing chronic pain inhibitors.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Jiwon Kim, Hyeoncheol Francis Son, Sungmin Hwang, Gyeongtaek Gong, Ja Kyong Ko, Youngsoon Um, Sung Ok Han, Sun-Mi Lee
Summary: This study improved the furfural tolerance of Y. lipolytica by enhancing its endogenous detoxification mechanism, leading to increased efficiency in producing lipids and other chemicals from lignocellulosic biomass.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Food Science & Technology
Naila Boby, Eon-Bee Lee, Muhammad Aleem Abbas, Na-Hye Park, Sam-Pin Lee, Md. Sekendar Ali, Seung-Jin Lee, Seung-Chun Park
Summary: FSC pretreatment reduces blood alcohol and acetaldehyde concentrations, modulates liver enzyme activities, increases antioxidant enzyme expression, and decreases inflammatory cytokine gene expression in the liver. Additionally, it shows no acute oral toxicity in female rats and may be beneficial for reducing alcohol-induced damage.
Article
Biochemistry & Molecular Biology
Alexandra N. Bogner, Kyle M. Stiers, Cole M. McKay, Donald F. Becker, John J. Tanner
Summary: ALDH4A1 is a dual substrate enzyme involved in the final steps of proline and hydroxyproline catabolism. The study found that trans-4-hydroxy-L-proline is the strongest inhibitor of ALDH4A1, with a competitive inhibition constant of 0.7 mM.
Article
Chemistry, Physical
Stefano Cattaneo, Sofia Capelli, Marta Stucchi, Filippo Bossola, Vladimiro Dal Santo, Eduard Araujo-Lopez, Dmitry I. Sharapa, Felix Studt, Alberto Villa, Alessandro Chieregato, Bart D. Vandegehuchte, Laura Prati
Summary: This study investigates the impact of side chains on the reactivity of aldehydes towards hydrogenation and hydrodeoxygenation, finding that pi-electron conjugation strongly influences the conversion of aldehydes to alcohols and hydrocarbons. Strong pi-electron conjugation, such as an aromatic ring, enables hydrogenation and hydrodeoxygenation of the carbonylic group, while molecules with no or weak pi-electron conjugation remain inactive. The results are supported by adsorption analyses and theoretical models, indicating that differences in adsorption mode and strength are not the decisive factors in carbonyl group conversion.
JOURNAL OF CATALYSIS
(2021)
Article
Biotechnology & Applied Microbiology
Neil D. Butler, Shelby R. Anderson, Roman M. Dickey, Priyanka Nain, Aditya M. Kunjapur
Summary: Aldehydes are important chemical targets for flavors and fragrances industry and synthetic intermediates due to their ability to form C-C bonds. This study identifies and addresses unexpected oxidation of aromatic aldehydes, and demonstrates that it can be slowed down by inactivating certain aldehyde dehydrogenase genes in E. coli. The newly engineered E. coli ROAR strain shows reduced oxidation and improved product titers in biocatalysis reactions involving aldehydes.
METABOLIC ENGINEERING
(2023)
Article
Multidisciplinary Sciences
Jinhong Liu, Shey-Li Lim, Jia Yi Zhong, Boon Leong Lim
Summary: Developed ratiometric biosensors for pyridine nucleotides to study energy metabolism in pollen tubes and the role of pollen plastids. Found that fermentation and pyruvate dehydrogenase bypass are not essential for pollen tube growth in Arabidopsis.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Peiyu Xu, Sijie Huang, Brian E. Krumm, Youwen Zhuang, Chunyou Mao, Yumu Zhang, Yue Wang, Xi-Ping Huang, Yong-Feng Liu, Xinheng He, Huadong Li, Wanchao Yin, Yi Jiang, Yan Zhang, Bryan L. Roth, H. Eric Xu
Summary: The dopaminergic system and its receptors (D1R to D5R) have important roles in the central nervous system. This study presents cryo-EM structures of all five subtypes of human dopamine receptors complexed with G protein and the pan-agonist rotigotine. The structures provide insight into rotigotine recognition, ligand polypharmacology, receptor activation, unique receptor subtype features, and G protein coupling specificity. This work offers a comprehensive set of structural templates for the development of specific ligands to target dopaminergic system-related CNS diseases.
Article
Biochemistry & Molecular Biology
Renjian Xiao, Zhuang Li, Shukun Wang, Ruijie Han, Leifu Chang
Summary: Cas12f, also known as Cas14, is a small type V-F CRISPR-Cas nuclease with unique substrate recognition and activation mechanisms. Cryo-EM structures revealed an asymmetric Cas12f dimer bound to sgRNA for dsDNA cleavage, highlighting the importance of coordinated conformational changes induced by substrate recognition. Additionally, truncated sgRNA was found to be active for target DNA cleavage, indicating potential genome editing applications for the miniature Cas12f.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
David A. Korasick, John J. Tanner
Summary: Certain mutations in the ALDH7A1 gene cause pyridoxine-dependent epilepsy (PDE), characterized by seizures and sometimes intellectual disability. These mutations, including over 70 missense mutations, have complex effects on the structure and catalytic activity of ALDH7A1. Mutations targeting active site residues and those remote from the site show varied impact, indicating the challenge in predicting the effects of missense mutations on enzyme function. Additional biophysical analyses of disease-causing mutations are necessary to develop predictive rules for enzyme structure and function.
Article
Biochemistry & Molecular Biology
Hao Li, Benedicta Forson, Meital Eckshtain-Levi, Hannah Valentino, Julia S. Martin del Campo, John J. Tanner, Pablo Sobrado
Summary: The study investigated the enzyme-enzyme interactions, catalytic reaction kinetics, and FAD binding properties of FRED and IBAH in the FRED:IBAH system. Results showed the formation of a protein-protein complex for direct transfer of reduced flavin from the reductase to the monooxygenase in this two-component system.
Article
Biochemistry & Molecular Biology
Ashley C. Campbell, Alexandra N. Bogner, Yizi Mao, Donald F. Becker, John J. Tanner
Summary: The study investigates the inhibition of PutA protein by proline stereoisomers and analogs through high-resolution crystal structures; the compounds are weak inhibitors with millimolar inhibition constants. The structural and kinetic data expand understanding of the interaction between proline-like molecules and GSALDH, providing insight into the relationship between stereochemistry and inhibitor affinity.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Virology
Ashley C. Campbell, John J. Tanner, Kurt L. Krause
Summary: This study presents a method for producing neuraminidase from a human cell line, which yielded high levels of soluble expression and supported high resolution crystal structure determination. The method is expected to be useful in further studies, such as the characterization of inhibitor binding.
Article
Chemistry, Multidisciplinary
Hannah Valentino, David A. Korasick, Tabbetha J. Bohac, Justin A. Shapiro, Timothy A. Wencewicz, John J. Tanner, Pablo Sobrado
Summary: Acinetobacter baumannii is an opportunistic pathogen with a high mortality rate, and the synthesis and uptake of iron-chelating siderophores Acinetobactin (Acb) and preacinetobactin (pre-Acb) are crucial for its virulence. The flavin-dependent siderophore-interacting protein (SIP) BauF plays a key role in the reduction of Fe(III) bound to Acb/pre-Acb and the release of Fe(II), with NAD(P)H not being its physiological partners. The structural and biochemical data presented validate the importance of BauF in A. baumannii iron assimilation, providing valuable information for drug design.
Article
Biochemistry & Molecular Biology
Sagar M. Patel, Javier Seravalli, Kyle M. Stiers, John J. Tanner, Donald F. Becker
Summary: L-Thioproline is a cyclic sulfur-containing analog of l-proline found in various organisms, and human PYCR isozymes 1 and 2 show significant dehydrogenase activity towards L-T4C. This suggests a new enzyme function for PYCRs in the metabolism of L-T4C, leading to cysteine formation.
Article
Biochemistry & Molecular Biology
David A. Korasick, Shelbi L. Christgen, Insaf A. Qureshi, Donald F. Becker, John J. Tanner
Summary: This study investigated the mechanism of proline utilization enzyme in bacteria using tunnel-blocking mutagenesis, revealing that Trp206 plays a crucial role in inhibiting the auxiliary tunnel 2a and impairing PRODH activity. Further experiments indicated that Trp206 may affect the binding of L-proline substrate and the closure of the PRODH active site by disrupting a specific ion pair.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Yizi Mao, Javier Seravalli, Thomas G. Smith, Martha Morton, John J. Tanner, Donald F. Becker
Summary: Thiazolidine carboxylates T4C and T2C, sulfur analogues of proline, are substrates for the enzyme PutA, which catalyzes their oxidation. The oxidation of T4C leads to cysteine formation, while oxidation of T2C generates a stable Delta(4)-thiazoline-2-carboxylate species.
Article
Chemistry, Organic
Alexandra N. Bogner, John J. Tanner
Summary: In this study, the inhibition of PRODH by 18 proline-like compounds was investigated to understand the structural and chemical features responsible for the affinity of the best-known inhibitor. The results revealed new structure-affinity relationships that could be utilized in the development of new inhibitor design strategies targeting PRODH.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Noah S. Lyons, John J. Tanner, Alexandra N. Bogner, Pablo Sobrado
Summary: Acinetobacter baumannii is a Gram-negative opportunistic pathogen that causes nosocomial infections. The rise of multidrug resistant strains of A. baumannii has limited the use of standard antibiotics, highlighting a need for new drugs that exploit novel mechanisms of pathogenicity. This study investigated FbsI, an N-hydroxylating monooxygenase involved in the biosynthesis of the major siderophore produced by A. baumannii. The results provide insights into the substrate recognition and catalytic cycle of FbsI, and have implications for understanding the pathogenic mechanisms and developing new antibiotics.
Article
Biochemistry & Molecular Biology
Kaylen R. Meeks, John J. Tanner
Summary: PYCRs are important enzymes involved in the biosynthesis of proline. They have been extensively studied in cancer, especially PYCR1, due to their role in altered metabolism. This study presents a method for expressing and purifying PYCR3 in E. coli. It shows that the activity of PYCR3 is dependent on the type of coenzyme used. Competitive inhibition assays were performed with proline analogs, and a higher selectivity for PYCR1 than PYCR3 was observed with N-formyl-L-proline.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Biochemistry & Molecular Biology
David A. Korasick, Luckio F. Owuocha, Pramod K. Kandoth, John J. Tanner, Melissa G. Mitchum, Lesa J. Beamer
Summary: This study investigates the effects of single variants P130R and N358Y in soybean SHMT8. The results demonstrate that these two variants have reduced catalytic activity compared to the susceptible Essex SHMT8, but are more active than the P130R/N368Y double variant. Additionally, the single variants lack THF-substrate inhibition, unlike Essex SHMT8. The crystal structures of the variants provide insights into the structural impacts of the mutations and allosteric regulation.
Article
Multidisciplinary Sciences
Cole E. E. McKay, Jianlin Cheng, John J. J. Tanner
Summary: The crystal structure of the domain of unknown function family 507 protein from Aquifex aeolicus was determined, revealing a Y-shaped α-helical structure with pseudo-twofold symmetry. The structures differ in their C-terminal arm rotation, suggesting a potential functional site.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
David P. Buckley, Marie E. Migaud, John J. Tanner
Summary: ox-NADs are redox inactive derivatives of NAD that accumulate in cells under stress and may act as potential inhibitors of enzymes. Molecular dynamics simulations reveal distinct conformational preferences of ox-NADs in solution, which could aid in identifying enzymes targeted by ox-NADs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Alexandra N. Bogner, Juan Ji, John J. Tanner
Summary: In this study, minimal PRODH domains have been engineered for inhibitor discovery, with designs containing approximately one-third of the PutA amino acid sequence and replacing a domain of PutA. The minimal PRODHs exhibit near wild-type enzymatic activity and are susceptible to known inhibitors and inactivators. Crystal structures of minimal PRODHs inhibited by specific compounds were determined, showing potential usefulness in chemical probe discovery.
PROTEIN ENGINEERING DESIGN & SELECTION
(2022)