Article
Biochemistry & Molecular Biology
Tatsiana Sushko, Anton Kavaleuski, Irina Grabovec, Anna Kavaleuskaya, Daniil Vakhrameev, Sergey Bukhdruker, Egor Marin, Alexey Kuzikov, Rami Masamrekh, Victoria Shumyantseva, Kouhei Tsumoto, Valentin Borshchevskiy, Andrei Gilep, Natallia Strushkevich
Summary: Research finds that RubB efficiently transfers electrons from cognate reductases to support bacterial CYPs activity, mutations on RubB surface do not significantly decrease CYPs activity, suggesting interactions are transient and nonspecific.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Olga Fedotovskaya, Ingrid Albertsson, Gustav Nordlund, Sangjin Hong, Robert B. Gennis, Peter Brzezinski, Pia Adelroth
Summary: The study identified a supercomplex composed of cyt. bc(1) and aa(3)-type cyt. c oxidase, and demonstrated the formation and activity of this supercomplex through various experiments. The potential role of membrane-anchored cyt. cy as a component in supercomplexes was also investigated in the study.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2021)
Article
Plant Sciences
Alejandro Torrado, Macarena Iniesta-Pallares, Adrian Velazquez-Campoy, Consolacion Alvarez, Vicente Mariscal, Fernando P. Molina-Heredia
Summary: This study investigates the function and classification of cytochrome c(6)-like proteins in photosynthetic cyanobacteria, and provides new data on the phylogeny, genome localization, and functional properties of these proteins. The findings suggest that cytochrome c(6)-like proteins may interact with the cytochrome b(6)f complex in a similar way as cytochrome c(6), and cytochrome c(6)D can react with the specific copper-oxidase in heterocysts.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Raul Covian, Lanelle O. Edwards, Bertrand M. Lucotte, Robert S. Balaban
Summary: The catalytic cycle of cytochrome c oxidase (COX) involves multiple intermediate states of the heme a3-CuB binuclear center. The fully reduced species of hemes a or a3, Peroxy (P), and Ferryl (F) intermediates are observed in respiration, while the R form is only detectable under nearly anoxic conditions. The reactions involving P and F species are dependent on transmembrane potential and slower than the oxidation of the R intermediate.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2023)
Article
Microbiology
Dawn E. Holmes, Jinjie Zhou, Toshiyuki Ueki, Trevor Woodard, Derek R. Lovley
Summary: The study demonstrates that the genetically tractable methanogen Methanosarcina acetivorans can grow via direct interspecies electron transfer (DIET) in coculture with Geobacter metallireducens. Transcriptomic analysis reveals higher expression of outer-surface multi-heme c-type cytochrome MmcA during DIET-based growth, while deletion of mmcA inhibits DIET. Additionally, the study provides insights into the potential role of aromatic amino acids in forming electrically conductive archaella and the involvement of membrane-bound complexes in energy production from carbon dioxide reduction during DIET.
Editorial Material
Biochemistry & Molecular Biology
F. Peter Guengerich
Summary: The paper introduces the concept of cytochrome b(5) as an auxiliary protein facilitating cytochrome P450 reactions, providing important insights for future research.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Biotechnology & Applied Microbiology
Jinjie Zhou, Dawn E. Holmes, Hai-Yan Tang, Derek R. Lovley
Summary: It is observed that Methanosarcina species can be divided into two distinct physiological groups, with type I focusing on H-2 production and consumption while type II avoids H-2 and possesses genes for an Rnf complex and the membrane-bound cytochrome MmcA. The distribution of Methanosarcina in different environments suggests that type I is suited for high-energy environments like anaerobic digesters, while type II is an adaptation to lower-energy environments like organic-poor anaerobic soils and sediments. This distinction is crucial in understanding the role of Methanosarcina in methanogenic environments, particularly in relation to H-2 metabolism.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2021)
Review
Biotechnology & Applied Microbiology
Toshiyuki Ueki
Summary: Geobacter species are important in environmental biogeochemical cycles and biotechnology applications due to their capability of direct EET with solid electron donors and acceptors. They have a large number of cytochromes encoded in their genomes, localized in various subcellular fractions and utilized differentially for EET with various electron donors and acceptors. Geobacter coordinates the cytochromes with other cellular components in an elaborate EET system to thrive in the environment.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2021)
Article
Cell Biology
Sue Ellen Brand, Martha Scharlau, Lois Geren, Marissa Hendrix, Clayre Parson, Tyler Elmendorf, Earl Neel, Kaila Pianalto, Jennifer Silva-Nash, Bill Durham, Francis Millett
Summary: Cytochrome c (Cc) has undergone accelerated evolution from anthropoid primates to humans, with several amino acid changes occurring near the binding site of the Cc:CcO complex. These changes affect the dissociation constant and the role of phosphorylation in regulating mitochondrial electron transport and membrane potential.
Article
Multidisciplinary Sciences
Agnes Moe, Justin Di Trani, John L. Rubinstein, Peter Brzezinski
Summary: Energy conversion in aerobic organisms involves electron transfer from low-potential donors to dioxygen through the membrane-bound respiratory chain. The formation of supercomplex CIII2CIV1/2 facilitates electron transfer by two-dimensional diffusion of cyt. c, increasing QH(2):O-2 oxidoreductase activity and suggesting a regulatory role for supercomplex formation in the respiratory chain.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Electrochemistry
Hans Schneider, Bin Lai, Jens O. Kromer
Summary: Substances inhibiting specific proteins involved in cellular electron transfer chains are used in biochemical research to investigate intracellular electron transfer routes and to redirect the electron fluxes. This also provides an in vivo approach to investigating the extracellular electron transfer (EET) mechanisms within and across biological membranes in bioelectrochemical research. However, the applicability of these specific inhibitors in electrochemical systems remains to be validated, particularly when aiming for (semi-)quantitative evaluation of the contribution of specific redox proteins to the EET. Here we conducted a systematic analysis of commonly used inhibitors and discovered several of them to be electrochemically active and thus capable of interfering with measurements in a bioelectrochemical reactor system in abiotic experiments. We also observed effects in vivo using a biophotovoltaics reactor with Synechocystis sp. PCC 6803 as a model system.
ELECTROCHEMISTRY COMMUNICATIONS
(2023)
Article
Microbiology
Robert C. Blake, John E. Shively, Russell Timkovich, Richard Allen White
Summary: This study investigated the genomic, structural, and kinetic characteristics of cytochrome 579 from Leptospirillum ferriphilum. The research revealed that only two out of the seven homologs of cytochrome 579 are expressed in each of the seven sequenced strains of L. ferriphilum. The findings suggest that cytochrome 579 may function as a periplasmic conduit for electron transfer in the aerobic iron respiratory chain of L. ferriphilum.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Environmental Sciences
Lei Chen, Mingpeng Wang, Yujie Feng, Xiaoyu Xu, Xiaobo Luo, Zhaojie Zhang
Summary: Xanthomonas, a common plant pathogen found in biocontaminated bioreactors, was found to exhibit characteristics such as reduction of metal Fe (III) and decolorization of methyl orange in vitro. This microorganism was able to generate bioelectricity and had two extracellular electron transfer pathways, with the indirect transfer method being dominant and faster than direct transfer. The study highlights a novel anaerobic mechanism for Xanthomonas survival during wastewater treatment and suggests potential strategies for preventing its growth.
SCIENCE OF THE TOTAL ENVIRONMENT
(2021)
Article
Environmental Sciences
Xing Yan, Jie Bu, Xiong Chen, Ming-Jun Zhu
Summary: Microbial extracellular respiration, including Fe(III) and electrode respiration, was observed in Thermoanaerobacterium thermosaccharolyticum MJ2. Comparative genomic analysis revealed the intra/extracellular electron transfer mechanism of MJ2, with hydrogenase and cytochrome c playing crucial roles. Moreover, the addition of exogenous Cyt-c significantly increased the bioelectricity generation by MJ2.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Article
Chemistry, Multidisciplinary
Andre Gemuende, Jonas Gail, Dirk Holtmann
Summary: Vibrio natriegens shows great potential as a biotechnological organism due to its fast growth, high productivity, and availability of genomic tools. It was found that V. natriegens possesses a similar extracellular electron transfer pathway as other electroactive organisms. This study demonstrated for the first time that V. natriegens can transfer electrons to an electrode through direct contact and an artificial redox mediator, highlighting its superior electron-transfer capabilities and metabolism.
Review
Pharmacology & Pharmacy
Kenneth A. Jacobson, Zhan-Guo Gao, Pierre Matricon, Matthew T. Eddy, Jens Carlsson
Summary: Caffeine and adenosine, along with their interaction with the A(2A) receptor, play crucial roles in the brain, particularly in the protection of aging brain and potential treatments for various diseases. Understanding the atomic-level interaction with the A(2A) receptor has led to the development of diverse drug molecules. The focus has expanded from neurodegenerative diseases to include cancer immunotherapy.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Benjamin Wiseman, Ram Gopal Nitharwal, Goeran Widmalm, Martin Hogbom
Summary: Lipopolysaccharides, crucial components of bacterial cell envelopes, are synthesized at the inner membrane through the Wzx/Wzy-dependent assembly pathway. The cryo-EM structure of intact E. coli WzzB provides insights into the transmembrane and cytoplasmic domains, as well as a conserved proline-rich segment near the C-terminal transmembrane helix.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Riccardo Diamanti, Vivek Srinivas, Annika Johansson, Anders Nordstrom, Julia J. Griese, Hugo Lebrette, Martin Hogbom
Summary: In this study, we characterized the ligands copurified with R2lox using mass spectrometry-based metabolomics. We also determined the crystal structures of two new homologs of R2lox, providing new insights into putative mechanisms regulating the function of the enzyme.
Article
Chemistry, Medicinal
Fabio Begnini, Stefan Geschwindner, Patrik Johansson, Lisa Wissler, Richard J. Lewis, Emma Danelius, Andreas Luttens, Pierre Matricon, Jens Carlsson, Stijn Lenders, Beate Konig, Anna Friedel, Peter Sjoe, Stefan Schiesser, Jan Kihlberg
Summary: Upregulation of the transcription factor Nrf2 by inhibiting the interaction with Keap1, its negative regulator, presents an opportunity for treating diseases caused by oxidative stress. In this study, we report the discovery of nanomolar Keap1 inhibitors derived from a natural product, which showed a 100-fold increase in inhibitory potency through structure-guided optimization. The nanomolar inhibitors positioned three pharmacophore units for productive interactions with Keap1, leading to significant changes in the thermodynamic profile. Optimizing the ligand resulted in displacement of a water molecule from the Keap1 binding site and alterations in the affinity between ligands, demonstrating the importance of considering hydration and flexibility of the Keap1 binding site when designing high-affinity ligands.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Andreas Luttens, Hjalmar Gullberg, Eldar Abdurakhmanov, Duy Duc Vo, Dario Akaberi, Vladimir O. Talibov, Natalia Nekhotiaeva, Laura Vangeel, Steven De Jonghe, Dirk Jochmans, Janina Krambrich, Ali Tas, Bo Lundgren, Ylva Gravenfors, Alexander J. Craig, Yoseph Atilaw, Anja Sandstrom, Lindon W. K. Moodie, Ake Lundkvist, Martijn J. van Hemert, Johan Neyts, Johan Lennerstrand, Jan Kihlberg, Kristian Sandberg, U. Helena Danielson, Jens Carlsson
Summary: Developing drug inhibitors targeting SARS-CoV-2 is crucial for saving lives and preparing for future outbreaks. Two virtual screening strategies were explored, resulting in the identification of compounds with inhibitory effects, including one compound with promising antiviral activity.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Agnes Moe, Terezia Kovalova, Sylwia Krol, David J. Yanofsky, Michael Bott, Dan Sjostrand, John L. Rubinstein, Martin Hogbom, Peter Brzezinski
Summary: The study identified a respiratory supercomplex CIII2CIV2 in the Corynebacterium glutamicum strain, which catalyzes the oxidation of menaquinol and reduction of dioxygen, providing energy for the bacteria's redox processes. The structure of the C. glutamicum supercomplex was determined using cryo-EM, revealing a dimer of respiratory complexes III and IV, connected by di-heme cyt. cc subunit for electron transfer and creating a proton transfer pathway.
Article
Multidisciplinary Sciences
Vincent Chaptal, Veronica Zampieri, Benjamin Wiseman, Cedric Orelle, Juliette Martin, Kim-Anh Nguyen, Alexia Gobet, Margot Di Cesare, Sandrine Magnard, Waqas Javed, Jad Eid, Arnaud Kilburg, Marine Peuchmaur, Julien Marcoux, Luca Monticelli, Martin Hogbom, Guy Schoehn, Jean-Michel Jault, Ahcene Boumendjel, Pierre Falson
Summary: This study resolved three outward-facing conformations of BmrA, a multidrug ABC transporter, using x-ray crystallography and cryo-electron microscopy. It was found that two R6G molecules bind to the drug-binding cavity, inducing a rearrangement of TM1-2 and highlighting local flexibility. Simulations showed that in the absence of R6G, the cavity quickly closed after drug release, while in the presence of R6G, the cavity remained open.
Article
Neurosciences
Wilber Romero-Fernandez, Jaume J. Taura, Rene A. J. Crans, Marc Lopez-Cano, Ramon Fores-Pons, Manuel Narvaez, Jens Carlsson, Francisco Ciruela, Kjell Fuxe, Dasiel O. Borroto-Escuela
Summary: The study demonstrates the role of A(2A)R in modulating the D2R-mGluR(5) heteromeric component, showing that A(2A)R and mGluR(5) can interact to influence D2R signaling, indicating integrative activity within higher-order heteroreceptor complexes.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Stefanie Kampen, David Rodriguez, Morten Jorgensen, Monika Kruszyk-Kujawa, Xinyan Huang, Michael Collins, Noel Boyle, Damien Maurel, Axel Rudling, Guillaume Lebon, Jens Carlsson
Summary: This study conducted molecular docking screens to identify allosteric modulators of the metabotropic glutamate receptor 5 (mGlu(5)). Four compounds with the highest affinities were confirmed to be negative allosteric modulators of mGlu(5) signaling.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sylwia Krol, Olga Fedotovskaya, Martin Hogbom, Pia Adelroth, Peter Brzezinski
Summary: This study investigates the electron and proton transfer kinetics of the M. smegmatis respiratory III2IV2 supercomplex upon reaction with molecular oxygen. The data show that the oxidation process of reduced CIV occurs in three components associated with the formation of the P, F, and O intermediates. Unlike canonical CIV, the P -> F and F -> O reactions are not pH dependent, and the proton uptake in CIV is significantly slower compared to canonical CIV due to the binding of a loop from the QcrB subunit of CIII at the D proton pathway of CIV.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2022)
Article
Biochemical Research Methods
Kristine Grave, Matthew D. Bennett, Martin Hogbom
Summary: This study presents a method for screening Mycobacterium tuberculosis membrane proteins in Escherichia coli Rosetta 2 (DE3) and Mycobacterium smegmatis mc24517, using a folding reporter GFP (frGFP) assay. It allows simultaneous screening of protein expression conditions for multiple targets. By studying 42 essential M. tuberculosis H37Rv helical transmembrane proteins, the study finds that basal expression of the lac operon in the T7-promoter expression system leads to high recombinant protein yield in M. smegmatis. The findings provide insights into expression conditions for M. tuberculosis membrane proteins.
PROTEIN EXPRESSION AND PURIFICATION
(2022)
Article
Biology
Juliane John, Oskar Aurelius, Vivek Srinivas, Patricia Saura, In-Sik Kim, Asmit Bhowmick, Philipp S. Simon, Medhanjali Dasgupta, Cindy Pham, Sheraz Gul, Kyle D. Sutherlin, Pierre Aller, Agata Butryn, Allen M. Orville, Mun Hon Cheah, Shigeki Owada, Kensuke Tono, Franklin D. Fuller, Alexander Batyuk, Aaron S. Brewster, Nicholas K. Sauter, Vittal K. Yachandra, Junko Yano, Ville Ri Kaila, Jan Kern, Hugo Lebrette, Martin Hogbom
Summary: Redox reactions play a central role in biochemistry and are controlled by protein structural changes. In this study, the authors utilized femtosecond crystallography to examine the structural rearrangements and crosstalk within the Bacillus cereus ribonucleotide reductase R2b-NrdI complex. They found that the flavin in the complex is under steric strain, which likely affects its redox properties and promotes superoxide generation. The redox state of the flavin also controls a binding site that is linked to the channel responsible for transporting superoxide species. These findings have important implications for understanding the control of reactive oxygen species and radical generation in protein R2b.
Correction
Chemistry, Medicinal
Fabio Begnini, Stefan Geschwindner, Patrik Johansson, Lisa Wissler, Richard J. Lewis, Emma Danelius, Andreas Luttens, Pierre Matricon, Jens Carlsson, Stijn Lenders, Beate Koenig, Anna Friedel, Peter Sjoe, Stefan Schiesser, Jan Kihlberg
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Albert Suades, Aziz Qureshi, Sarah E. McComas, Mathieu Coincon, Axel Rudling, Yurie Chatzikyriakidou, Michael Landreh, Jens Carlsson, David Drew
Summary: The authors have optimized a transport assay in liposomes to study glucose transporters (GLUTs) and provide insights into other membrane transport proteins. GLUTs play a crucial role in glucose homeostasis and their dysfunction is linked to diseases like diabetes and cancer. However, transport assays using purified GLUTs have been challenging, which hampers in-depth mechanistic investigations.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Benjamin Wiseman, Goeran Widmalm, Martin Hoegbom
Summary: Through cryo-electron microscopy, it was discovered that the co-polymerase WzzE, responsible for length modulation of the enterobacterial common antigen, consists of eight subunits arranged in alternating up-down conformations. The clashing helical faces between adjacent protomers contribute to the alternating arrangement of the L4 loops, creating a dynamic environment for polysaccharide elongation. This study provides insight into the mechanisms of lipopolysaccharide elongation and length regulation.
COMMUNICATIONS BIOLOGY
(2023)