Article
Biochemistry & Molecular Biology
Andrea Dali, Thomas Gabler, Federico Sebastiani, Alina Destinger, Paul Georg Furtmueller, Vera Pfanzagl, Maurizio Becucci, Giulietta Smulevich, Stefan Hofbauer
Summary: Coproporphyrin ferrochelatases (CpfCs) are enzymes that catalyze the penultimate step in the coproporphyrin-dependent heme biosynthesis pathway. The discovery of the correct substrate for these ferrochelatases and the characterization of their binding mode provide valuable insights into the iron insertion process. This knowledge is essential for understanding the preconditions and mechanisms of iron insertion in CpfCs.
Article
Chemistry, Multidisciplinary
Katherine W. Rush, Karsten A. S. Eastman, William M. Kincannon, Ninian J. Blackburn, Vahe Bandarian
Summary: This study examines the role of additional auxiliary clusters (ACs) in two enzymes, PapB and Tte1186, that catalyze thioether cross-link formation in ribosomally synthesized and post-translationally modified peptides (RiPPs). It is shown that both enzymes tolerate substitution of SeCys instead of Cys at the cross-linking site and interact with ACs in the Michaelis complex. The identity of the AC is determined through site-directed deletion in Tte1186.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Emily C. Ulrich, Catherine L. Drennan
Summary: Cobalamin-dependent S-adenosyl-L-methionine radical methylases are enzymes that use a dual-cofactor system to perform challenging radical methylation reactions. They are part of a larger subgroup of enzymes that also perform difficult ring contractions and radical rearrangements. This subgroup represents a largely unexplored reservoir of diverse chemistry. This Perspective article highlights the efforts to understand the function, mechanism, and structure of TsrM, an unexpected nonradical methylase in this subgroup, and discusses recent achievements in characterizing radical methylase subgroup members.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Plant Sciences
Yu Li, Wangdan Xiong, Feng He, Tianxiong Qi, Zhen Sun, Yuchen Liu, Shiqie Bai, Honglun Wang, Zhenying Wu, Chunxiang Fu
Summary: The down-regulation of PvSAMS in switchgrass can reduce the contents of SAM, G-lignins, and S-lignins, leading to the accumulation of methionine and glucoside derivatives of caffeoyl alcohol, and resulting in brownish stems. Transcriptomic analysis shows that most sulfur deficiency-responsive genes are differentially expressed in the transgenic switchgrass, leading to an increase in total sulfur content.
JOURNAL OF EXPERIMENTAL BOTANY
(2022)
Article
Multidisciplinary Sciences
Suppachai Srisantitham, Edward D. Badding, Daniel L. M. Suess
Summary: This study successfully incorporated Fe-57 into specific sites of the nitrogenase cofactor L-cluster, providing crucial insights into its electronic structure and biosynthesis. It introduces postbiosynthetic modification as a promising strategy for further studies on nitrogenase cofactors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Daniel W. Bak, Eranthie Weerapana
Summary: This study describes a chemoproteomic strategy that monitors changes in the reactivity of Fe-S cysteine ligands to inform on Fe-S cluster occupancy and demonstrates its utility in Escherichia coli. The results show global disruptions in Fe-S incorporation in cells cultured under iron-depleted conditions, identify Fe-S client proteins reliant on scaffold, carrier, and chaperone proteins within the Isc Fe-S biogenesis pathway, and identify two previously unannotated Fe-S proteins, TrhP and DppD.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Organic
Jing-Jing Ai, Bei-Bei Liu, Jian Li, Fei Wang, Cheng-Mi Huang, Weidong Rao, Shun-Yi Wang
Summary: An iron-sulfur complex formed by mixing FeCl3 with S-3(center dot-) from K2S is developed for selective aerobic oxidation of terminal alkenes. The reaction can be carried out under an atmosphere of O-2, and can proceed on a gram scale, expanding the application of S-3(center dot-) in organic synthesis. This study also encourages further exploration of the application of Fe-S catalysts in organic reactions.
Article
Chemistry, Multidisciplinary
Ronald A. Besandre, Zhang Chen, Ian Davis, Jiawei Zhang, Mark Walter Ruszczycky, Aimin Liu, Hung-wen Liu
Summary: HygY is a SPASM/twitch radical SAM enzyme catalyzing the C2'-epimerization of galacamine during hygromycin B biosynthesis. The biochemical and structural analysis of reaction products confirmed this activity, and also revealed a latent dehydrogenase activity in this enzyme. This discovery offers insights into the mechanistic features distinguishing oxidative versus redox-neutral SPASM/twitch enzymes and the evolution of new enzyme activities.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Biochemistry & Molecular Biology
Vivian Robert Jeyachandran, Amie K. Boal
Summary: Radical S-adenosylmethionine (SAM) enzymes use a common catalytic core for various transformations. They bind a Fe4S4 cluster through a tri-cysteine motif, and some enzymes also bind additional metal cofactors. Recent studies have revealed the structures of these enzymes with methylcobalamin or additional iron-sulfur clusters as cosubstrates. These auxiliary units are anchored by N-and C-terminal domains that have significant variations in size and topology. However, they all share a common surface for docking the auxiliary cofactors. Interaction with iron-sulfur cluster assembly proteins or downstream scaffold proteins is important for catalysis in sulfur insertion and metallocofactor assembly systems. The structures of these complexes represent new frontiers in the structural analysis of radical SAM enzymes.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
Review
Cell Biology
Jonathan Dietz, Jennifer L. Fox, Oleh Khalimonchuk
Summary: Cellular iron homeostasis and mitochondrial iron homeostasis are interdependent, where mitochondria import iron to form clusters and heme, and supply the cell with heme for essential functions. Impairment in iron homeostasis can lead to various human diseases. Iron is stored and trafficked through carefully orchestrated processes intracellularly and within mitochondria.
Article
Chemistry, Multidisciplinary
Yu Tian, Xi-Tao Li, Ji-Ren Liu, Jian Cheng, Ang Gao, Ning-Yuan Yang, Zhuang Li, Kai-Xin Guo, Wei Zhang, Han-Tao Wen, Zhong-Liang Li, Qiang-Shuai Gu, Xin Hong, Xin-Yuan Liu
Summary: The study demonstrates an enantioconvergent radical C(sp(3))-S cross-coupling reaction using chiral tridentate anionic ligands and Cu(I) catalysts. This method provides a broad substrate scope, high enantioselectivity, and access to useful alpha-chiral alkyl organosulfur compounds with different sulfur oxidation states, serving as a complementary approach to known asymmetric C(sp(3))-S bond formation methods.
Article
Multidisciplinary Sciences
Takashi Fujishiro, Kyosei Takaoka
Summary: The authors present an X-ray crystal structure of a class III hybrid cluster protein (HCP) that is structurally similar to Ni, Fe-carbon monoxide dehydrogenases (CODHs), enabling conclusions to be drawn regarding the structural evolution of the HCP/CODH superfamily.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Alan H. Baik, Augustinus G. Haribowo, Xuewen Chen, Bruno B. Queliconi, Alec M. Barrios, Ankur Garg, Mazharul Maishan, Alexandre R. Campos, Michael A. Matthay, Isha H. Jain
Summary: Oxygen is toxic across all three domains of life, but the molecular mechanisms underlying this toxicity are largely unknown. In this study, we investigate the cellular pathways affected by excess oxygen and find that it destabilizes a specific subset of Fe-S cluster (ISC)-containing proteins, leading to impaired synthesis and repair functions. We show that electron transport chain (ETC) is the most vulnerable to damage, resulting in decreased mitochondrial oxygen consumption and further tissue damage. This research has important implications for hyperoxia-related pathologies.
Article
Biochemistry & Molecular Biology
Filipa Calisto, Smilja Todorovic, Ricardo O. Louro, Manuela M. Pereira
Summary: This study used nanodiscs and liposomes technology to investigate the ACIII activity in membrane-mimicking systems of Rhodothermus marinus, and also studied the interaction of ACIII with menaquinone, HiPIP, cytochrome c, and caa3 oxygen reductase.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2023)
Review
Plant Sciences
Diego F. Gomez-Casati, Maria Busi, Julieta Barchiesi, Maria A. Pagani, Noelia S. Marchetti-Acosta, Agustina Terenzi
Summary: Iron and sulfur are essential elements for organisms, forming Fe-S clusters that play key roles in various cellular processes. Information on genes and proteins involved in Fe-S cluster assembly in green algae, particularly in mitochondrial pathways, is limited and requires further investigation.
Article
Biochemistry & Molecular Biology
Lisete Galego, Susana Barahona, Celia V. Romao, Cecilia M. Arraiano
Summary: This study demonstrated via in vivo and mass spectrometry that BolA is phosphorylated at four highly conserved protein positions. Mutating these positions affected BolA functions related to cell wall synthesis and division, morphology, permeability, motility, and biofilm formation. Phosphorylation was shown to be crucial in modulating BolA activity as a transcription factor and regulator of cell morphology and biofilm development.
Article
Chemistry, Analytical
Susana A. Lobo, Paulina Baczyk, Brigitte Wyss, Jasmin C. Widmer, Lidia P. Jesus, Joana Gomes, Ana P. Batista, Steffen Hartmann, Paul Wassmann
Summary: Identification of molecular liabilities and implementation of mitigation strategies are essential for pharmaceutical companies developing therapeutic proteins. Streamlined processes like developability assessment are used in selecting the fittest candidate, especially in the field of monoclonal antibodies. Different protein modalities may require a paradigm change towards candidate enabling, with early assessment of liabilities being crucial for project success.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2021)
Article
Multidisciplinary Sciences
Tessa R. Young, Maria Alessandra Martini, Andrew W. Foster, Arthur Glasfeld, Deenah Osman, Richard J. Morton, Evelyne Deery, Martin J. Warren, Nigel J. Robinson
Summary: Researchers have developed a metalation-calculator to elucidate metal occupancies in cells, showing how competition and variable metal availability affect metal binding to three different proteins in vivo.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Liliana S. O. Silva, Pedro M. Matias, Celia V. Romao, Ligia M. Saraiva
Summary: In this study, a previously unrecognized link between the di-iron protein YtfE and the major bacterial system for iron-sulfur cluster assembly was identified in E. coli. The promotion of Fe-S cluster formation in IscU by YtfE was found to require two glutamates, E125 and E159, with E125 being crucial for iron export. This study provides evidence for the key role of RICs as bacterial iron donor proteins in the biogenesis of Fe-S clusters.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Raquel R. Lopes, Catarina S. Tome, Roberto Russo, Roberta Paterna, Joao Leandro, Nuno R. Candeias, Lidia M. D. Goncalves, Miguel Teixeira, Pedro M. F. Sousa, Rita C. Guedes, Joao B. Vicente, Pedro M. P. Gois, Paula Leandro
Summary: Phenylketonuria (PKU) is a genetic disease caused by deficient activity of human phenylalanine hydroxylase (hPAH) and protein misfolding is recognized as the main underlying pathogenic mechanism of PKU. 3-hydroxyquinolin-2(1H)-one derivatives were found to act as protectors of hPAH enzyme activity, affecting the coordination of the non-heme ferric center at the enzyme active site. These stabilizing compounds were shown to be outcompeted by the natural substrate l-phenylalanine, but two compounds functionally stabilized hPAH by maintaining protein activity.
Review
Biochemistry & Molecular Biology
Sofia S. Mendes, Vanessa Miranda, Ligia M. Saraiva
Summary: Hydrogen sulfide and carbon monoxide can have beneficial or harmful effects on organisms depending on their concentrations, with humans and some bacteria producing small amounts of these compounds. Research has focused on how bacteria produce and utilize H2S and CO, as well as their potential antimicrobial properties at higher concentrations and how microbial systems detect and survive toxic levels of these gases. Additionally, their antimicrobial properties against human pathogens have been highlighted when produced endogenously by the host or released by external chemical donors.
Article
Chemistry, Physical
Maria C. Martins, Susana F. Fernandes, Bruno A. Salgueiro, Jessica C. Soares, Celia Romao, Claudio M. Soares, Diana Lousa, Filipe Folgosa, Miguel Teixeira
Summary: Flavodiiron proteins are a family of enzymes with nitric oxide and/or oxygen reductase activities. Mutants with altered conserved residues showed reduced oxygen reductase activity and in some cases completely abolished NO reductase activity, possibly due to changes in predicted structures affecting hydration and hydrogen bonds.
Article
Microbiology
Catarina Amaral, Cristina Teixeira Vicente, Soraia Marques Caetano, Ana Gaspar-Cordeiro, Yang Yang, Peter Cloetens, Celia V. Romao, Claudina Rodrigues-Pousada, Catarina Pimentel
Summary: Ccc1 plays a critical role in iron storage and detoxification in yeast, and the discovery of s-Ccc1 highlights its potential to function under iron overload conditions even when its expression is repressed.
Review
Chemistry, Inorganic & Nuclear
Jordi Zamarreno Beas, Marco A. M. Videira, Ligia M. Saraiva
Summary: Haem b and sirohaem are two important prosthetic groups in bacterial proteins, synthesized through complex pathways with divergences at the formation of uroporphyrinogen III. The biosynthesis of these tetrapyrroles involves unstable or potentially hazardous intermediates and end-products, requiring tight control of cellular metabolic fluxes.
COORDINATION CHEMISTRY REVIEWS
(2022)
Article
Microbiology
Freddy Bunbury, Evelyne Deery, Andrew P. Sayer, Vaibhav Bhardwaj, Ellen L. Harrison, Martin J. Warren, Alison G. Smith
Summary: Cobalamin (vitamin B-12) is a co-factor for essential metabolic reactions in multiple eukaryotic taxa, but can only be produced by prokaryotes. Bacteria can colonize algae, forming stable communities that exchange compounds such as B-12. Bacteria that release more B-12 may be selected for in symbiotic relationships with B-12-dependent algae.
ENVIRONMENTAL MICROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Liliana S. O. Silva, Pedro M. Matias, Celia Romao, Ligia M. Saraiva
Summary: Repair of Iron Center proteins (RIC) are a family of di-iron proteins found widely in microbes. This review summarizes the data on microbial RICs, including their gene regulation and contribution to pathogenic bacteria survival. The focus is on Escherichia coli RIC, with extensive biochemical characterization and new structural data featuring a di-manganese site. The networking of protein interactions involving RIC and its proposed physiological role as an iron donor for repairing damaged iron-sulfur centers are also described.
Editorial Material
Microbiology
Michael D. Paxhia, Mingzhi Liang, Martin J. Warren
Summary: Recent research highlights the role of the shell protein PduB in the internalization process of enzyme cargo in BMCs.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Markus Wiedemair, Christoph Kieninger, Klaus Wurst, Maren Podewitz, Evelyne Deery, Michael D. Paxhia, Martin J. Warren, Bernhard Kraeutler
Summary: In this study, we synthesized a new B-12 derivative, AcRhbl, by replacing the cobalt-center of AcCbl with its rhodium homologue. The structures of AcCbl and AcRhbl were analyzed in various conditions, revealing extensive structural similarity. AcRhbl, classified as an 'antivitamin B-12', joins the small group of B-12 mimics and shows potential as a selective inhibitor of key cellular processes in biological and biomedical applications.
HELVETICA CHIMICA ACTA
(2023)
Article
Plant Sciences
Andrew P. Sayer, Marcel Llavero-Pasquina, Katrin Geisler, Andre Holzer, Freddy Bunbury, Gonzalo Mendoza-Ochoa, Andrew D. Lawrence, Martin J. Warren, Payam Mehrshahi, Alison G. Smith
Summary: Microalgae are important in global ecosystems and require vitamin B-12 for growth. This study identifies a protein, CBA1, that is essential for B-12 uptake in microalgae. Through targeted knockouts and mutagenesis, the researchers demonstrate that CBA1 is necessary for B-12 uptake in two different microalgae species. The study also shows that CBA1 is present in other eukaryotes, indicating its conserved role in the biological kingdom.
Article
Microbiology
Sandra M. Carvalho, Claudia S. Freitas, Ana S. Oliveira, Ligia M. Saraiva
Summary: The study revealed that Staphylococcus aureus relies on Hmp to play an important role in biofilm formation, especially under nitrosative stress conditions. The hmp mutant showed significantly impaired early stage biofilm development capacity, which was fully restored by trans-complementation of Hmp. Additionally, coculture studies indicated that the hmp mutant had a lower capacity to develop biofilm biomass when compared with the wild type in the presence of cells from the host innate immune system.
FEMS MICROBIOLOGY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Trang Van Tran, Hoa Nguyen, Luyen Vu, ChangWoo Lee
Summary: Glutaredoxin 3 (Grx3) is a redox protein that maintains structural integrity and glutathione (GSH) binding capabilities across different temperatures. This study investigates the roles of specific bonds in Grx3's structure and function, and how psychrophilic Grx3 variants adapt to cold environments. The highly conserved Arg51-Asp69 salt bridge and Gln56-His63 hydrogen bond are crucial for stabilizing the structure and catalytic activity of Grx3. Psychrophilic variants of Grx3 have adapted to cold environments by reducing GSH binding and increasing structural flexibility.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Amanda Lais de Souza Coto, Arthur Alexandre Pereira, Sabrina Dorta Oliveira, Milene Nobrega de Oliveira Moritz, Arthur Moraes Franco da Rocha, Paulo Roberto Dores-Silva, Noeli Soares Melo da Silva, Ana Rita de Araujo Nogueira, Lisandra Marques Gava, Thiago Vagas Seraphim, Julio Cesar Borges
Summary: J-domain proteins form a large molecular chaperone family involved in proteostasis processes, with hDjC20 playing a vital role in mitochondria and being heavily influenced by the presence of Zn+2.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Meiling Zhang, Jiaxiang Zhang, Yan Liang, Shicheng Tian, Shuyang Xie, Tong Zhou, Qin Wang
Summary: This study determined the crystal structures of RGLG2 VWA domain in Arabidopsis thaliana, revealing that Ca2+ ions act as regulators and affect the conformational change of RGLG2-VWA domain.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Alexandra Bork, Sander H. J. Smits, Lutz Schmitt
Summary: This study reveals the structure and calcium ion binding properties of CBL1 protein, and proposes a binding model of CBL1 for Ca2+. Additionally, it provides preliminary insights into the formation of the dimer interface of CBL1.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Evgeniia V. Leisi, Andrey V. Moiseenko, Sofia S. Kudryavtseva, Denis V. Pozdyshev, Vladimir I. Muronetz, Lidia P. Kurochkina
Summary: The pathogenesis of prion diseases involves the transformation of prion protein into an insoluble form. This study found that two phage chaperonins can promote the fibrillation of prion protein in an ATP-dependent manner, resulting in the formation of less toxic large clusters. These fibrils differ in morphology and properties from those formed spontaneously in acidic pH with denaturants.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Gaurab Chowdhury, Saroj Biswas, Yuthika Dholey, Puja Panja, Sumit Das, Subrata Adak
Summary: Magnesium is an important divalent cation for regulating enzyme activity. The binding of Mg2+ through the PAS domain inhibits phosphoglycerate kinase (PGK) activity in LmPAS-PGK at neutral pH, but PGK activity is derepressed at acidic pH. Mutation studies revealed that the Asp-4 residue is crucial for Mg2+ binding at neutral pH.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Shima Ghaedizadeh, Majid Zeinali, Bahareh Dabirmanesh, Behnam Rasekh, Khosrow Khajeh, Ali Mohammad Banaei-Moghaddam
Summary: Implementing hyperthermostable carbonic anhydrases into CO2 capture and storage technologies can increase the rate of CO2 absorption from industrial flue gases. This study successfully improved the thermostability of a known hyperthermostable carbonic anhydrase through rational engineering of a single-point mutation.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Khaled A. Elnahriry, Dorothy C. C. Wai, Lauren M. Ashwood, Muhammad Umair Naseem, Tibor G. Szanto, Shaodong Guo, Gyorgy Panyi, Peter J. Prentis, Raymond S. Norton
Summary: Sea anemone venom contains a peptide called Tst2, which shows sequence similarity to peptides that interact with various ion channels. Recombinant Tst2 was successfully produced and its structure and function were studied. The results showed that Tst2 is an inhibitor of the TRPV1 channel.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)