Article
Chemistry, Physical
Sebastian A. Diaz, Priscilla Choo, Eunkeu Oh, Kimihiro Susumu, William P. Klein, Scott A. Walper, David A. Hastman, Teri W. Odom, Igor L. Medintz
Summary: Using nanoparticles as templates can increase the kinetic rates of enzymes, especially in multi-enzyme cascades where enzymes on the same nanoparticle provide advantages such as substrate channeling. The size and curvature of nanoparticles have a significant impact on the kinetics of cascade reactions, with different shaped nanoparticles achieving equivalent enhancements in kinetics.
Article
Chemistry, Physical
Yan Xie, Scott Calabrese Barton
Summary: This study combines computational methods to investigate the transport mechanism of glucose-6-phosphate in an enzyme complex bridged by poly-arginine peptides, suggesting that poly-arginine peptides may be more efficient in transporting reactants compared to poly-lysine. This work presents a potential improvement for the electrostatic channeling of anionic intermediates.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Agricultural Engineering
Misa Mojca Cajnko, Jost Oblak, Miha Grilc, Blaz Likozar
Summary: Enzymes play a crucial role in lignin valorization, with different enzymes involved in various elementary reaction mechanisms. Degradation of lignin depends on enzyme activity and the interaction with proteins in ways that target specific covalent bonds in lignin. Various factors influence enzymatic activity, which must be taken into consideration for optimal functionality and synthesis yields.
BIORESOURCE TECHNOLOGY
(2021)
Article
Engineering, Environmental
Huiling Jia, Shengwei Huang, Shuo Cheng, Xiwen Zhang, Xue Chen, Yisen Zhang, Jun Wang, Lifang Wu
Summary: This study systematically analyzed the mechanisms of selenium reduction by the probiotic bacterium Bacillus subtilis both in vivo and in vitro, revealing multiple key genes and pathways involved. The findings provide new insights for the treatment of selenite.
JOURNAL OF HAZARDOUS MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Tyler B. Alt, Matthew R. Hoag, Graham R. Moran
Summary: This article presents the first comprehensive kinetic investigation of a bacterial form of DPD, revealing its similarity to the mammalian form in terms of mechanism but with distinct aspects in substrate roles.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Review
Biochemistry & Molecular Biology
Zhaobing Ding, Russell E. Ericksen, Qian Yi Lee, Weiping Han
Summary: Dysregulated cellular energetics is a recognized hallmark of cancer, with metabolic reprogramming playing a crucial role in sustaining cancer cell proliferation. The proline metabolism pathway is implicated in promoting tumorigenesis in various cancer types, including liver cancer. Research on the impact of proline metabolism on liver cancer and other cancers, as well as the related mechanisms, is a priority in current therapeutic studies.
Article
Pharmacology & Pharmacy
Marco Albrecht, Yuri Kogan, Dagmar Kulms, Thomas Sauter
Summary: Dabrafenib inhibits cell proliferation in metastatic melanoma, but its effectiveness is limited due to drug resistance and relapse. Using a pharmacokinetic model, we predict the drug concentrations after long-term accumulation and found that it has limited effect on melanoma cells.
Article
Biochemistry & Molecular Biology
Bharath Srinivasan
Summary: The kinetics parameters during the interaction between drugs and targets play an important role in drug optimization and dosing decisions.
Article
Biochemistry & Molecular Biology
Janez Smerkolj, Jure Stojan, Aljosa Bavec, Marko Golicnik
Summary: Human paraoxonase-1 (PON1), the most studied member of the paraoxonases family, catalyzes the hydrolysis of various substrates. PON1 is linked to oxidative stress-related diseases, and analyzing progress curves reveals that it self-inactivates during catalytic turnover. Human serum albumin or surfactants can protect PON1 from inactivation.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Andrea Moreno, Victor Taleb, Maria Sebastian, Ernesto Anoz-Carbonell, Marta Martinez-Julvez, Milagros Medina
Summary: The biosynthesis of flavins involves two enzymes, RFK and FMNAT, with different structural and functional characteristics in bacteria and mammals. Prokaryotic FADS, including those from pathogens, show variability in less conserved regions, allowing for alternative strategies in flavin homeostasis. Targeting FADSs from pathogens could lead to species-specific inhibitors.
Article
Plant Sciences
Merve Seven, U. Cem Derman, Andrew J. Harvey
Summary: Xyloglucan endotransglycosylase/hydrolase (XTH) enzymes have been found to exhibit broad substrate specificities, including cellulose analogues and mixed-link beta-glucans, in addition to the standard xyloglucan. This discovery opens up a wide range of potential roles for these enzymes, both within plants and in various industries. Furthermore, genome screening and expression analyses suggest that the XTH genes in the "ancestral" clades are unique to angiosperms, predominantly expressed in reproductive tissues, leading to the proposal of renaming this phylogenetic group as the group-IV clade.
Article
Endocrinology & Metabolism
Jeffrey M. McManus, Yoon-Mi Chung, Nima Sharifi
Summary: Conversion of adrenally produced DHEA to DHT is a key mechanism in castration resistance of prostate cancer. This study investigated the kinetics of these reactions in cells and found that low concentrations of DHEA primarily underwent 3 beta HSD-catalyzed conversion to Delta(4)-androstenedione, while high concentrations underwent 17 beta HSD-catalyzed conversion to Delta(5)-androstenediol.
Article
Biochemistry & Molecular Biology
Zhitao Mao, Xin Zhao, Xue Yang, Peiji Zhang, Jiawei Du, Qianqian Yuan, Hongwu Ma
Summary: Genome-scale metabolic models (GEMs) are widely used for predicting the phenotypes of microorganisms. However, the lack of other constraints in the stoichiometric model often limits the accessibility of the metabolic solution space. In this study, we developed an enzyme-constrained metabolic network model (ECMpy) and applied it to Escherichia coli (E. coli) to improve the accuracy of phenotype predictions. By considering the total enzyme amount constraint, protein subunit composition, and enzyme kinetic parameters, we were able to better predict the overflow metabolism and growth rates of E. coli. The enzyme-constrained model revealed the tradeoff between enzyme usage efficiency and biomass yield, providing valuable insights for metabolic engineering.
Article
Nanoscience & Nanotechnology
Shelby Hooe, Joyce Breger, Scott Dean, Kimihiro Susumu, Eunkeu Oh, Scott Walper, Gregory A. Ellis, Igor L. Medintz
Summary: Cell-free enzymatic cascades are efficient, selective, and environmentally sustainable strategies for synthesizing complex organic molecules. Immobilizing enzymes onto nanoparticle surfaces can enhance catalytic rate and enzymatic efficiency, and enable substrate channeling in coupled activity.
ACS APPLIED NANO MATERIALS
(2022)
Article
Chemistry, Physical
Tobias M. Milzarek, Sebastian Schuler, Anke Matura, Tobias A. M. Gulder
Summary: This study systematically investigated the effects of structural changes to the natural substrate sorbicillin on its activity, providing important insights into its promiscuity and facilitating the efficient preparation of unnatural sorbicillinoids. Additionally, the total syntheses of several natural and unnatural sorbicillinoids were reported.
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)
Review
Biochemistry & Molecular Biology
Alexandra N. Bogner, Kyle M. Stiers, John J. Tanner
Summary: Proline metabolism plays a significant role in cancer cells, involving upregulation of proline biosynthetic genes and the dual function of proline catabolic enzyme in promoting cancer and apoptosis. The cycling of proline impacts cellular growth and death pathways. PYCR, the last enzyme in proline biosynthesis, is crucial for the proline metabolic cycle and has been shown to be widely upregulated in various cancer types.
Article
Biochemistry & Molecular Biology
Ashley C. Campbell, Austin R. Prater, Alexandra N. Bogner, Thomas P. Quinn, Kent S. Gates, Donald F. Becker, John J. Tanner
Summary: The discovery of a new class of PRODH inactivator that covalently and irreversibly modifies the FAD in a light-dependent manner provides a new approach for developing photopharmacological drugs targeting cancer cells. The inactivation process involves exposure to bright white light, leading to irreversible loss of enzyme activity and potential photosensitivity of cancer cells.
ACS CHEMICAL BIOLOGY
(2021)
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
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
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)