Article
Biochemistry & Molecular Biology
Jessica A. Gable, Thomas L. Poulos, Alec H. Follmer
Summary: P450lin has higher selectivity for its non-native redox partner Arx than its native partner Pdx, and Pdx shows higher activity when mutated, indicating that the interactions between P450lin and its redox partners are different from P450cam-Pdx.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Freeborn Rwere, Sangchoul Im, Lucy Waskell
Summary: By altering the 140s FMN binding loop of CYPOR, the activity with cyt P450s can be affected, with the mutant activity primarily determined by its ability to reduce ferric cyt P450. The different behaviors of the mutants are mainly due to the altered structure and mobility of the loop.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Physical
Yumiao Ma, Aqeel A. Hussein
Summary: We present a strategy to tune the catalytic behavior of the pincer-Co catalyst by investigating the effect of partners such as (18-crown-6)K+, W(CO)(3), and W(PMe3)(3) on the nitrile hydroboration reaction. The partner's influence on the cobalt center's electron-richness and the donor ability of the pincer ligand is revealed through pi-coordination. These findings suggest a notable partner effect that can be explored by experimentalists to tune the reactivity of catalysts without ligand modification.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Review
Biochemistry & Molecular Biology
Manuel J. Mallen-Ponce, Samuel Gamez-Arcas, Maria Esther Perez-Perez
Summary: Autophagy is a catabolic pathway that maintains cellular homeostasis by degrading and recycling cellular materials. It involves the formation of autophagosomes, double-membrane vesicles that engulf the material to be degraded and recycled. However, the mechanisms and regulation of autophagy in photosynthetic organisms like microalgae are not fully understood.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Cara L. Loomis, Simone Brixius-Anderko, Emily E. Scott
Summary: The study finds that adrenodoxin can regulate the ligand binding and catalytic activity of CYP11B1 enzyme, reducing the dissociation constant of substrate binding and the inhibitory effect of inhibitors. Comparison between different CYP11B enzymes reveals significant differences in the effects of adrenodoxin, likely due to variations in their sequences and structures. These findings underscore the importance of considering P450/redox partner interactions when evaluating new inhibitors.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Chao-Lai Tong, Xiu-Hua Xu, Feng-Ling Qing
Summary: Efficient heptafluoroisopropoxylation reactions were achieved through the invention of a series of redox-active N-OCF(CF3)(2) reagents. Various substrates can undergo direct heptafluoroisopropoxylation to yield products in moderate to excellent yields.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Multidisciplinary Sciences
Florencia Tomasina, Jennyfer Martinez, Ari Zeida, Maria Laura Chiribao, Veronica Demicheli, Agustin Correa, Celia Quijano, Laura Castro, Robert H. Carnahan, Paige Vinson, Matt Goff, Tracy Cooper, W. Hayes McDonald, Natalie Castellana, Luciana Hannibal, Paul T. Morse, Junmei Wan, Maik Huttemann, Ronald Jemmerson, Lucia Piacenza, Rafael Radi
Summary: Cytochrome c (cyt c) undergoes reversible conformational changes under biologically relevant conditions, but revealing these alternative conformations at the cell and tissue level is challenging. This study successfully resurrected a monoclonal antibody (mAb) that recognizes a key conformational change in cyt c and showed similar performance to the original mAb. Using this antibody, alternative conformations of cyt c were identified in cells under oxidative or senescence-induced challenge, and these conformations translocated to the nucleus without causing apoptosis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
David C. Lamb, Tatiana Y. Hargrove, Bin Zhao, Zdzislaw Wawrzak, Jared Goldstone, William David Nes, Steven L. Kelly, Michael R. Waterman, John J. Stegeman, Galina Lepesheva
Summary: Sterol biosynthesis in Methylococcus capsulatus involves a simplified pathway with the key step of sterol 14 alpha-demethylation catalyzed by CYP51. The structure of CYP51fx from M. capsulatus is the first of a bacterial sterol biosynthetic enzyme, suggesting a common evolutionary origin of eukaryotic and bacterial CYP51s. Bioinformatic analysis reveals the presence of CYP51 genes in over 1,000 bacteria, supporting the idea that early eukaryotes may have recruited CYP51 from bacterial sources.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Biochemistry & Molecular Biology
Irina F. Sevrioukova
Summary: CYP3A7 is a fetal/neonatal liver enzyme involved in estriol synthesis and xenobiotic metabolism, with reduced ligand binding capacity compared to adult liver enzyme CYP3A4. Structural analysis of CYP3A7 reveals decreased flexibility and altered interactions in the active site, limiting protein plasticity and potentially impacting reactivity and oxidation of substrates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Yuchen Wang, Xiaowei Gong, Fan Li, Shasha Zuo, Minggang Li, Jiangyuan Zhao, Xiulin Han, Mengliang Wen
Summary: The study focused on biosynthesis of santalenes and santalols from sandalwood essential oil using synthetic biology strategy in S. cerevisiae, achieving high yields by integrating optimized P450-CPR redox system and downregulating ERG9 gene. The research provides a feasible solution for optimal biosynthesis of santalols.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Xiaodong Zhang, Yun Hu, Wei Peng, Chenghua Gao, Qiong Xing, Binju Wang, Aitao Li
Summary: In this study, the oxidizing activity of CYP109B1 was reconstituted by coupling redox pairs or fusing it to the reductase domain of two self-sufficient P450 enzymes. The best redox pair for CYP109B1 was found to be Fdr_0978/Fdx_1499 from Synechococcus elongatus, showing over 99% conversion with 73% 15 beta selectivity for testosterone. The enzyme displayed good activity and selectivity toward testosterone derivatives, with a shift in selectivity for specific substrates.
FRONTIERS IN CHEMISTRY
(2021)
Review
Biotechnology & Applied Microbiology
Behnaz Nowrouzi, Leonardo Rios-Solis
Summary: The increasing trend towards producing cytochrome P450-mediated natural products in microbial systems is due to the challenging nature of organic chemistry methods. Manipulating the redox potential in microbial chassis for natural product synthesis is limited, as the crucial role of redox state in regulating P450 biocatalysis has been underestimated.
CRITICAL REVIEWS IN BIOTECHNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Takashi Harimoto, Tomoki Tadokoro, Soichiro Sugiyama, Takanori Suzuki, Yusuke Ishigaki
Summary: The concept of a domino reaction has been successfully applied to redox chemistry in this study, where a change in molecular conformation was used to trigger a domino redox reaction. This provides a new approach and method for developing novel redox reactions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Simone Brixius-Anderko, Emily E. Scott
Summary: Primary aldosteronism, the most common form of secondary hypertension, has limited treatment options. Research suggests that the interaction between adrenodoxin and CYP11B2 may have an allosteric component, providing potential for new treatment approaches for primary aldosteronism.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Michele F. Caliandro, Felix Schmalbein, Luca Matteo Todesca, Matthias Moergelin, Maryam Rezaei, Juliane Meissner, Isabel Siepe, Julius Grosche, Albrecht Schwab, Johannes A. Eble
Summary: Integrin-mediated cell contacts with the extracellular matrix (ECM) play essential roles in cellular adhesion, force transmission, and migration. The binding activities of integrins and their cellular functions are regulated by various effectors, such as divalent cations and redox-active compounds. This study investigates the interplay between the Ca2+ binding site and redox-regulation within the hinge region of the integrin alpha 7 subunit, revealing their mutual dependence in adhesion strength and cell migration. Furthermore, protein-chemical analyses suggest that the activation of integrin via the alpha hinge is primed by the formation of cysteine pair-based crosslinkage, followed by Ca2+ complexation, resulting in altered cell functions mediated by integrin and ECM ligand binding.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Rachel C. Steinhardt, Colin M. Rathbun, Brandon T. Krull, Jason M. Yu, Yuhang Yang, Brian D. Nguyen, Jake Kwon, David C. McCutcheon, Krysten A. Jones, Filipp Furche, Jennifer A. Prescher
Article
Chemistry, Medicinal
Scott A. Hollingsworth, Brian D. Nguyen, Georges Chreifi, Anton P. Arce, Thomas L. Poulos
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2017)
Article
Multidisciplinary Sciences
Ned Van Eps, Christian Altenbach, Lydia N. Caro, Naomi R. Latorraca, Scott A. Hollingsworth, Ron O. Dror, Oliver P. Ernst, Wayne L. Hubbell
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Review
Neurosciences
Scott A. Hollingsworth, Ron O. Dror
Article
Biochemistry & Molecular Biology
Kaavya Krishna Kumar, Moran Shalev-Benami, Michael J. Robertson, Hongli Hu, Samuel D. Banister, Scott A. Hollingsworth, Naomi R. Latorraca, Hideaki E. Kato, Daniel Hilger, Shoji Maeda, William I. Weis, David L. Farrens, Ron O. Dror, Sanjay V. Malhotra, Brian K. Kobilka, Georgios Skiniotis
Article
Multidisciplinary Sciences
Thomas A. Chew, Benjamin J. Orlando, Jinru Zhang, Naomi R. Latorraca, Amy Wang, Scott A. Hollingsworth, Dong-Hua Chen, Ron O. Dror, Maofu Liao, Liang Feng
Article
Multidisciplinary Sciences
Scott A. Hollingsworth, Brendan Kelly, Celine Valant, Jordan Arthur Michaelis, Olivia Mastromihalis, Geoff Thompson, A. J. Venkatakrishnan, Samuel Hertig, Peter J. Scammells, Patrick M. Sexton, Christian C. Felder, Arthur Christopoulos, Ron O. Dror
NATURE COMMUNICATIONS
(2019)
Article
Chemistry, Physical
Brian D. Nguyen, Guo P. Chen, Matthew M. Agee, Asbjorn M. Burow, Matthew P. Tang, Filipp Furche
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2020)
Article
Chemistry, Physical
Sree Ganesh Balasubramani, Guo P. Chen, Sonia Coriani, Michael Diedenhofen, Marius S. Frank, Yannick J. Franzke, Filipp Furche, Robin Grotjahn, Michael E. Harding, Christof Haettig, Arnim Hellweg, Benjamin Helmich-Paris, Christof Holzer, Uwe Huniar, Martin Kaupp, Alireza Marefat Khah, Sarah Karbalaei Khani, Thomas Mueller, Fabian Mack, Brian D. Nguyen, Shane M. Parker, Eva Perlt, Dmitrij Rappoport, Kevin Reiter, Saswata Roy, Matthias Rueckert, Gunnar Schmitz, Marek Sierka, Enrico Tapavicza, David P. Tew, Christoph van Wuellen, Vamsee K. Voora, Florian Weigend, Artur Wodynski, Jason M. Yu
JOURNAL OF CHEMICAL PHYSICS
(2020)
Article
Biochemistry & Molecular Biology
Naomi R. Latorraca, Matthieu Masureel, Scott A. Hollingsworth, Franziska M. Heydenreich, Carl-Mikael Suomivuori, Connor Brinton, Raphael J. L. Townshend, Michel Bouvier, Brian K. Kobilka, Ron O. Dror
Article
Chemistry, Medicinal
Brendan Kelly, Scott A. Hollingsworth, David C. Blakemore, Robert M. Owen, R. Ian Storer, Nigel A. Swain, Deniz Aydin, Rubben Torella, Joseph S. Warmus, Ron O. Dror
Summary: Biased agonists selectively stimulate certain signaling pathways controlled by GPCRs to maximize efficacy and minimize side effects. Designing biased agonists for the mu OR remains challenging due to unclear ligand-mediated interactions and differences in interaction with the binding pocket may lead to distinct bias profiles.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Physical
Jason M. Yu, Brian D. Nguyen, Jeffrey Tsai, Devin J. Hernandez, Filipp Furche
Summary: This Perspective discusses recent progress in selfconsistent calculations of ground-state energies using the random phase approximation (RPA) within the context of (generalized) Kohn-Sham (KS) density functional theory. The concept of functional selfconsistency (FSC) is introduced along with the development of the generalized KS semicanonical projected RPA (GKS-spRPA) method, which shows improvements in densities, binding energy curves, and molecular properties. The differences between KS and interacting densities without FSC and the performance of GKS-spRPA suggest that the KS potential for explicitly potential-dependent density functionals should be defined via the FSC condition.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Chemistry, Multidisciplinary
Lucy E. Darago, Monica D. Boshart, Brian D. Nguyen, Eva Perlt, Joseph W. Ziller, Wayne W. Lukens, Filipp Furche, William J. Evans, Jeffrey R. Long
Summary: Researchers have synthesized and characterized a series of trinuclear 4d-4f compounds with highly polarizable MoS 4 3- bridging units. The compounds exhibit specific metal-to-metal charge transfer properties, significant unpaired electron density, and ferromagnetic exchange behavior, providing a potential route for the design of new nd-4f single-molecule magnets and bulk magnetic materials.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Multidisciplinary Sciences
Joseph M. Paggi, Julia A. Belk, Scott A. Hollingsworth, Nicolas Villanueva, Alexander S. Powers, Mary J. Clark, Augustine G. Chemparathy, Jonathan E. Tynan, Thomas K. Lau, Roger K. Sunahara, Ron O. Dror
Summary: The study presents a statistical framework that combines physics-based and ligand-based models for predicting ligand pose and virtual screening of drug candidates. This combined model improves prediction accuracy across different drug target families and offers opportunities to enhance prediction of various ligand properties through custom machine-learning approaches.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)