Bacterial transcriptional repressor NrdR – a flexible multifactorial nucleotide sensor DOI Creative Commons
Inna Rozman Grinberg, Ornella Bimaï, Saher Shahid

et al.

FEBS Journal, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

NrdR is a bacterial transcriptional repressor consisting of zinc (Zn)‐ribbon domain followed by an ATP‐cone domain. Understanding its mechanism action could aid the design novel antibacterials. binds specifically to two “NrdR boxes” upstream ribonucleotide reductase operons, which Escherichia coli has three: nrdHIEF, nrdDG and nrdAB, in last we identified new box. We show that E. (EcoNrdR) similar binding strength all three sites when loaded with ATP plus deoxyadenosine triphosphate (dATP) or equivalent diphosphate combinations. No other combination adenine nucleotides promotes DNA. present crystal structures EcoNrdR–ATP–dATP EcoNrdR–ADP–dATP, are first high‐resolution NrdR. have also determined cryo‐electron microscopy DNA‐bound filaments EcoNrdR–ATP. Tetrameric forms EcoNrdR involve alternating interactions between pairs Zn‐ribbon domains ATP‐cones. The reveal considerable flexibility relative orientation ATP‐cones vs domains. structure shows significant conformational rearrangements Zn‐ribbons accompany DNA while retain same orientation. In contrast, ATP‐loaded sequester DNA‐binding residues such they unable bind Our results, previous structural biochemical study, point highly flexible that, correct nucleotides, adapt optimal promoter‐binding conformation.

Language: Английский

Structure and function of haemoglobins DOI
David A. Gell

Blood Cells Molecules and Diseases, Journal Year: 2017, Volume and Issue: 70, P. 13 - 42

Published: Oct. 31, 2017

Language: Английский

Citations

209

Drop-on-demand sample delivery for studying biocatalysts in action at X-ray free-electron lasers DOI
Franklin D. Fuller, Sheraz Gul, Ruchira Chatterjee

et al.

Nature Methods, Journal Year: 2017, Volume and Issue: 14(4), P. 443 - 449

Published: Feb. 27, 2017

Language: Английский

Citations

176

Archaeal phospholipids: Structural properties and biosynthesis DOI

Antonella Caforio,

Arnold J. M. Driessen

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Journal Year: 2016, Volume and Issue: 1862(11), P. 1325 - 1339

Published: Dec. 20, 2016

Language: Английский

Citations

104

Quantifying structural relationships of metal-binding sites suggests origins of biological electron transfer DOI Creative Commons
Yana Bromberg, Ariel A. Aptekmann, Yannick Mahlich

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(2)

Published: Jan. 14, 2022

[Figure: see text].

Language: Английский

Citations

42

Structural phylogenetics unravels the evolutionary diversification of communication systems in gram-positive bacteria and their viruses DOI Creative Commons
David Moi, Charles Bernard, Martin Steinegger

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 21, 2023

Abstract Recent advances in AI-based protein structure modeling have yielded remarkable progress predicting structures. Since structures are constrained by their biological function, geometry tends to evolve more slowly than the underlying amino acids sequences. This feature of could principle be used reconstruct phylogenetic trees over longer evolutionary timescales sequence-based approaches, but until now a reliable structure-based tree building method has been elusive. Here, we demonstrate that structure-informed phylogenies can outperform sequence-only ones not only for distantly related proteins also, remarkably, closely ones. is achieved inferring from using local structural alphabet, an approach robust conformational changes confound traditional distance measures. As illustration, decipher diversification particularly challenging family: fast-evolving RRNPPA quorum sensing receptors enabling gram-positive bacteria, plasmids and bacteriophages communicate coordinate key behaviors such as sporulation, virulence, antibiotic resistance, conjugation or phage lysis/lysogeny decision. The advent high-accuracy phylogenetics enables myriad applications across biology, uncovering deeper relationships, elucidating unknown functions, refining design bioengineered molecules.

Language: Английский

Citations

31

Chlorophyll Degradation and its Physiological Function DOI

Ayumi Tanaka,

Hisashi Itô

Plant and Cell Physiology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 22, 2024

Research on chlorophyll degradation has progressed significantly in recent decades. In the 1990s, structure of linear tetrapyrrole, which is unambiguously a product, was determined. From 2000s until 2010s, major enzymes involved were identified, and pheophorbide oxygenase/phyllobilin pathway established. This encompasses several steps: (1) initial conversion b to 7-hydroxymethyl a; (2) (3) dechelation pheophytin (4) dephytylation (5) opening macrocycle yield red catabolite; (6) catabolite phyllobilins. converts potentially harmful into safe molecules phyllobilins, are stored central vacuole terrestrial plants. The expression chlorophyll-degrading mediated by various transcription factors influenced light conditions, stress, plant hormones. Chlorophyll differently regulated different organs developmental stages initiation induces further enzymes, resulting acceleration degradation. initially considered last reaction senescence; however, plays crucial roles enhancing senescence, degrading chlorophyll-protein complexes, forming photosystem II, maintaining seed quality. Therefore, controlling important agricultural applications.

Language: Английский

Citations

14

NrdR in Streptococcus and Listeria spp.: DNA Helix Phase Dependence of the Bacterial Ribonucleotide Reductase Repressor DOI Creative Commons
Saher Shahid, Mateusz Bałka, Daniel Lundin

et al.

Molecular Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

ABSTRACT NrdR is a universal transcriptional repressor of bacterial genes coding for ribonucleotide reductases (RNRs), essential enzymes that provide DNA building blocks in all living cells. Despite its prevalence, the mechanism has been scarcely studied. We report biochemical, biophysical, and bioinformatical characterization binding sites from two major pathogens phylum Bacillota Listeria monocytogenes Streptococcus pneumoniae . consists Zn‐ribbon domain followed by an ATP‐cone domain. show it forms tetramers bind to when loaded with ATP dATP, but if only ATP, various oligomeric complexes unable DNA. The DNA‐binding site L. pair boxes separated 15–16 bp, whereas S. , are unusually long spacers 25–26 bp. This observation triggered comprehensive study four NrdRs Escherichia coli Streptomyces coelicolor series dsDNA fragments where were 12–27 vitro results confirmed vivo E. revealed binds most efficiently there integer number turns between center boxes. facilitates prediction genomes suggests conserved throughout It sheds light on RNR regulation since does not occur eukaryotes, opens way development novel antibiotics.

Language: Английский

Citations

1

Ribonucleotide Reductase Requires Subunit Switching in Hypoxia to Maintain DNA Replication DOI Creative Commons
Iosifina P. Foskolou, Christian Jorgensen, Katarzyna B. Leszczyńska

et al.

Molecular Cell, Journal Year: 2017, Volume and Issue: 66(2), P. 206 - 220.e9

Published: April 1, 2017

Cells exposed to hypoxia experience replication stress but do not accumulate DNA damage, suggesting sustained replication. Ribonucleotide reductase (RNR) is the only enzyme capable of de novo synthesis deoxyribonucleotide triphosphates (dNTPs). However, oxygen an essential cofactor for mammalian RNR (RRM1/RRM2 and RRM1/RRM2B), leading us question source dNTPs in hypoxia. Here, we show that RRM1/RRM2B retaining activity therefore favored over RRM1/RRM2 order preserve ongoing avoid accumulation damage. We found two distinct mechanisms by which RRM2B maintains hypoxic identified responsible residues RRM2B. The importance response tumor further illustrated correlation its expression with a signature patient samples roles growth radioresistance. Our data provide mechanistic insight into biology, highlighting as hypoxic-specific, anti-cancer therapeutic target.

Language: Английский

Citations

86

New tricks for the glycyl radical enzyme family DOI
Lindsey R. F. Backman, Michael A. Funk,

Christopher D. Dawson

et al.

Critical Reviews in Biochemistry and Molecular Biology, Journal Year: 2017, Volume and Issue: 52(6), P. 674 - 695

Published: Sept. 13, 2017

Glycyl radical enzymes (GREs) are important biological catalysts in both strict and facultative anaerobes, playing key roles the human microbiota environment. GREs contain a backbone glycyl that is post-translationally installed, enabling radical-based mechanisms. function several metabolic pathways including mixed acid fermentation, ribonucleotide reduction anaerobic breakdown of nutrient choline pollutant toluene. By generating substrate-based species within active site, enable C-C, C-O C-N bond breaking formation steps otherwise challenging for nonradical enzymes. Identification previously unknown family members from genomic data determination structures well-characterized have expanded scope GRE-catalyzed reactions as well defined features catalysis. Here, we review mechanisms characterized GREs, classifying into five categories. We consider open questions about each GRE classes evaluate tools available to interrogate uncharacterized GREs.

Language: Английский

Citations

85

The TIM Barrel Architecture Facilitated the Early Evolution of Protein-Mediated Metabolism DOI Creative Commons
Aaron D. Goldman,

Joshua T. Beatty,

Laura F. Landweber

et al.

Journal of Molecular Evolution, Journal Year: 2016, Volume and Issue: 82(1), P. 17 - 26

Published: Jan. 1, 2016

The triosephosphate isomerase (TIM) barrel protein fold is a structurally repetitive architecture that present in approximately 10 % of all enzymes. It generally assumed this ubiquity modern proteomes reflects an essential historical role early protein-mediated metabolism. Here, we provide quantitative and comparative analyses to support several hypotheses about the importance TIM architecture. An information theoretical analysis structures supports hypothesis could arise more easily by duplication recombination compared other mixed α/β structures. We show enzymes corresponding most taxonomically broad superfamilies also have broadest range functions, often aided metal nucleotide-derived cofactors are thought reflect earlier stage metabolic evolution. By comparison putatively ancient architectures, find functional diversity proteins cannot be explained simply their antiquity. Instead, breadth functions can explained, part, incorporation cofactors, trend does not appear shared general. These results simple functionally general may arisen evolution biosynthesis provided ideal scaffold facilitate transition from ribozymes, peptides, geochemical catalysts

Language: Английский

Citations

79