Protein‐Protein Stabilization in VIVO/8‐Hydroxyquinoline–Lysozyme adduct: A Spectroscopic, Crystallographic, and Computational Study

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: unknown

Published: June 24, 2024

Abstract The binding of the potential drug [V IV O(8‐HQ) 2 ], where 8‐HQ is 8‐hydroxyquinolinato, with hen egg white lysozyme (HEWL) was evaluated through spectroscopic (electron paramagnetic resonance, EPR, and UV‐visible), spectrometric (electrospray ionization‐mass spectrometry, ESI‐MS), crystallographic (X‐ray diffraction, XRD), computational (DFT docking) studies. ESI‐MS indicates interaction O(8‐HQ)(H O)] + (H species HEWL. Room temperature EPR spectra suggest both covalent non‐covalent two different V‐containing fragments. XRD analyses confirm these findings, showing that interacts covalently solvent exposed Asp119, while cis ‐[V non‐covalently Arg128 Lys96 from a symmetry mate. to Asp119 favored by π‐π contact Trp62 H‐bond Asn103 symmetry‐related molecule. Additionally, V O Asp48 other fragments Arg5, Cys6, Glu7 are revealed. Molecular docking that, in absence interactions occurring at protein‐protein interface close Glu35 or Asp52 should be preferred. Such stabilization could more common than what believed up today, least solid state, considered characterization metal‐protein adducts.

Language: Английский

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Linking the transcriptome to physiology: response of the proteome of cupriavidus metallidurans to changing metal availability

Metallomics, Journal Year: 2024, Volume and Issue: 16(12)

Published: Nov. 19, 2024

Abstract Cupriavidus metallidurans CH34 is a metal-resistant bacterium. Its metal homeostasis based on flow equilibrium of ion uptake and efflux reactions, which adapts to changing concentrations within an hour. At high concentrations, upregulation the genes for systems occurs minutes. Here, we investigate changes in bacterial proteome accompanying these genetic physiological events after 1.5 cell duplications, took 3 h. To that end, C. its plasmid-free derivative, AE104, either were challenged with toxic mix or cultivated under metal-starvation conditions, followed by bottom-up proteomics. When metal-shocked -starved cells compared their respective controls, 3540 proteins changed abundance, 76% appearing one, but not other, condition; remaining 24% up- downregulated. Metal-shocked strains had adjusted proteomes combat stress. The most prominent polypeptides products plasmid-encoded metal-resistance determinants strain CH34, particularly CzcCBA transenvelope system. Moreover, influence antisense transcripts was also revealed. In one specific example, impact asRNA abundance gene could be demonstrated this yielded new insights into function transmembrane complex ZniCBA conditions starvation.

Language: Английский

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Chemistry meets biology in the coordination dynamics of metalloproteins

Journal of Inorganic Biochemistry, Journal Year: 2023, Volume and Issue: 251, P. 112431 - 112431

Published: Nov. 19, 2023

Metal sites in proteins are often presented an idealized way that does not capture the intrinsic dynamic behavior of protein or extrinsic factors affect changes coordination metal ion biological space and time. The bioinorganic chemistry possible healthy diseased living organisms is limited by prevailing pH values, redox potentials, availability concentrations ions ligands. Changes any these parameters protein-protein protein-ligand interactions can result differences type bound, occupancy, number geometry. This article addresses plasticity complexity when considered. It uses three examples zinc with sulfur donor atoms from cysteines mammalian proteins: alcohol dehydrogenases, metallothioneins, transporters ZnT (SLC30A) family. Coordination dynamics has different purposes; dehydrogenases for to perform its roles catalytic cycle, metallothioneins serving as a buffer, sensing moving them through thus membranes. Defining chemical determine will inform future investigations metalloproteins.

Language: Английский

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Exonic splicing code and coordination of divalent metals in proteins

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 52(3), P. 1090 - 1106

Published: Dec. 6, 2023

Abstract Exonic sequences contain both protein-coding and RNA splicing information but the interplay of protein code is complex poorly understood. Here, we have studied traditional auxiliary codes human exons that encode residues coordinating two essential divalent metals at opposite ends Irving–Williams series, a universal order relative stabilities metal–organic complexes. We show encoding Zn2+-coordinating amino acids are supported much less by motifs than Ca2+. The handicap former compensated stronger splice sites uridine-richer polypyrimidine tracts, except for position –3 to 3′ junctions. However, Ca2+ Zn2+ exhibit close-to-constitutive in multiple tissues, consistent with their critical importance metalloprotein function relatively small fraction expendable, alternatively spliced exons. These results indicate constraints imposed metal coordination spheres on been efficiently overcome plasticity exon–intron architecture ensure adequate expression.

Language: Английский

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TheBacillus subtilis yqgC-sodAoperon protects magnesium-dependent enzymes by supporting manganese efflux

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 16, 2024

Abstract Microbes encounter a myriad of stresses during their life cycle. Dysregulation metal ion homeostasis is increasingly recognized as key factor in host-microbe interactions. Bacterial tightly regulated by dedicated metalloregulators that control uptake, sequestration, trafficking, and efflux. Here, we demonstrate deletion the Bacillus subtilis yqgC-sodA (YS) complex operon, but not individual genes, causes hypersensitivity to manganese (Mn). YqgC an integral membrane protein unknown function SodA Mn-dependent superoxide dismutase (MnSOD). The YS strain has reduced expression two Mn efflux proteins, MneP MneS, consistent with observed sensitivity. accumulated high levels Mn, had increased reactive radical species (RRS), broad metabolic alterations can be partially explained inhibition Mg-dependent enzymes. Although operon efflux-deficient mneP mneS double mutant both accumulate have similar perturbations they also display phenotypic differences. Several mutations suppressed intoxication did benefit mutant. Further, mutant, strain, was alleviated Mg-dependent, chorismate-utilizing enzymes m enaquinone, s iderophore, tryptophan (MST) family. Therefore, despite similarities, sensitivity mutants results from distinct enzymatic vulnerabilities. Importance Bacteria require multiple trace ions for survival. Metal relies on storage, proteins. occurs when perturbed often enzyme mis-metalation. In , MnSOD most abundant Mn-containing important oxidative stress resistance. report novel roles co-regulated protein, YqgC, homeostasis. Loss (but mutations) prevents efficient proteins leads large-scale perturbation metabolome due enzymes, including MST (menaquinone, siderophore, tryptophan) family

Language: Английский

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Cyanobacterial Zur: Zinc‐Sensing Transcriptional Regulators

Encyclopedia of Inorganic and Bioinorganic Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 13

Published: April 1, 2024

Abstract Zur (zinc uptake regulator) proteins are the most widespread bacterial zinc‐sensing transcriptional regulators, being encoded in majority of sequenced genomes. They work predominantly as repressors zinc genes when a bacterium's environment is abundant. Zinc scarcity turn leads to de‐repression these genes, which increased uptake. More recently, several have also been shown activators transcription, but mechanism(s) for this type regulation not fully understood. Several 3D structures available, including those from actinobacterium Streptomyces coelicolor, pathogenic Mycobacterium tuberculosis and Xanthomonas campestris , marine cyanobacterium Synechococcus sp. WH8102. The SynZur protein latter photosynthetic organism focus entry. In contrast many other bacteria harbor at least two sole transcription factor cyanobacterium. Like proteins, it regulates znuABC encode ABC‐type systems located inner membrane. Uniquely, however, activates metallothionein ( bmtA ). small cysteine‐rich high capacity bind up four ions normally regulated by SmtB family, response excess. ability upregulate production storage upon encountering ‘luxury’ appears enable WH8102 related oligotrophic strains populate ecological niches that poor inorganic nutrients may experience episodic rises levels.

Language: Английский

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Metalloproteome plasticity - a factor in bacterial pathogen adaptive responses?

PubMed, Journal Year: 2024, Volume and Issue: 8(1), P. 57 - 60

Published: Feb. 22, 2024

Through homeostatic processes, bacterial cells maintain intracytoplasmic metal ions at concentrations which enable the 'correct' to be inserted into an enzyme, thereby ensuring function. However, fluctuations in ion mean that under different conditions certain enzymes may contain metals their active site. This perspective describes examples of such cases and suggests metalloproteome plasticity contribute dynamic adaptation pathogens stresses host environment.

Language: Английский

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Probing metalloenzyme dynamics in living systems: Contemporary advances in fluorescence imaging tools and applications

Current Opinion in Chemical Biology, Journal Year: 2024, Volume and Issue: 81, P. 102475 - 102475

Published: June 11, 2024

Language: Английский

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Exchange of Equatorial Ligands in Protein-bound Paddlewheel Ru₂⁵⁺ Complexes: New Insights form X-ray Crystallography and Quantum Chemistry

Inorganic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

The reactivity of [Ru 2 Cl(D- p -CNPhF)(O CCH 3 ) ] n (D- -CNPhF − = N , ′-bis(4-cyanophenyl)formamidinate) with the model protein RNase A has been investigated by X-ray crystallography and Quantum Chemistry.

Language: Английский

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Nobel symposium #168 Visions of bio‐inorganic chemistry: metals and the molecules of life

FEBS Letters, Journal Year: 2023, Volume and Issue: 597(1), P. 3 - 5

Published: Jan. 1, 2023

The Nobel symposium “Visions of bio-inorganic chemistry: metals and the molecules life” was held at end May 2022 in Stockholm, Sweden. current special issue FEBS Letters contains contributions from speakers and, even though only representing a small part field, illustrate its immense breadth, progress potential. study biology, bioinorganic chemistry, is inherently multidisciplinary drawing on methods expertise physics, inorganic biochemistry biology. This continuously expands with recent tools including de-novo protein design numerous big data -omics methods, just to name few. overall goal answer central scientific questions regarding acquisition utilization radicals, as well address most pressing challenges for humankind by understanding, utilizing, mimicking extending this chemistry. As so many other meetings, had been postponed due Covid-19 pandemic. Before pandemic, 2019 biology GRC, Harry Gray painted picture that stuck me. He concluded we have four bulk resources earth will forever: nitrogen (N2), carbon dioxide (CO2), water (H2O) sunlight. In sustainable future, has no alternative but produce food, materials energy require those solar photons. From chemist's perspective, forms formidable challenge; these are notoriously inert compounds resist attempts be converted into anything more complex. Luckily, observing nature, know it possible. Photosynthesis fixation two basic reactions enter subsequent enormous chemical space potential key combine redox chemistry radicals exquisite specificity selectivity enzymes. It estimated almost half all enzymes metal cofactors function [[1]]. describes number such examples. Lubitz, Yano Siegbahn [[2-4]] contribute three fascinating accounts how work using various experimental techniques together theory now allows us paint detailed photosystem II functions oxygenic photosynthesis. reaction fascinated scientists since first clues obtained Joliot 1969, flash-induced period-four oscillations oxygen evolution [[5]]. level understanding achieved wonderful testament nature field. also computational studies nitrogenase, an enzyme further described perspective Rees [[6]]. gives account knowledge system evolved early experiments informed great approaches. advances certainly astonishing still, nitrogenase retains some secrets mechanism beautifully complicated 7Fe-9S-C-Mo-homocitrate cofactor. research article, coworkers [[7]] describe Flavocytochrome P450 Bacillus megaterium, heme capable hydroxylating non-activated aliphatic lipids. focus is, however, not substrate per se rather mechanisms put place protect self-inactivation runaway oxidizing species when oxidation Solomon provides binuclear copper monooxygenases [[8]]. These constitute families varied functions. article state characterization ternary intermediate Tyrosinase contributed longstanding monooxygenation monooxygenases. Klinman [[9]] paints metalloenzymes can activated dynamics interplay between addressed novel theoretical Broderick Hoffman review vast “radical SAM” family proteins [[10]]. Enzymes utilizing 4Fe-4S cluster S-adenosyl-methionine perform hugely diverse set radical-based reactions. Recent discoveries revealed “Ω” mechanistic analogies adenosyl cobalamine (coenzyme B12) cofactor, establishing common principles enzymatic radical generation. Ferredoxins another large iron–sulfur proteins. Lill reviews mitochondrial 2Fe-2S ferredoxins their very biochemistry, identified than century ago, while others recently discovered [[11]]. While perhaps well-known example use ions plethora essential roles signaling, electron transfer, regulation, transport maintenance osmotic pressure electrochemical gradients. provided Banci Butler [[12, 13]] provide perspectives acquired transported cell, fundamental requirement any function. papers serve new mining genome sequences in-cell spectroscopic insight until completely out reach. Robinson [[14]] takes next step cell acquire correct competition metal-binding lies both specific general control chaperones strict availability. Lippard intriguing mobile zinc influences amplitude sensory response nervous [[15]]. Analytical form Zn2+-specific chelators developed processes effects described. Giese architecture long-distance transfer pathways [[16]]. encompasses distances unused thinking about biochemical context, example, cable bacteria conduct electrons over cm-distances connect donors acceptors aquatic sediments. Bren Casini [[17, 18]] examples applications bioinspired systems. considers storage finding inspiration proton reduction nature. discusses supramolecular coordination complexes create versatile biomedical drug delivery imaging. define state-of-the-art, importantly, across sub-fields directions possibilities future. Reading papers, I cannot marvel progress. hope they ideas combinations probe deeper properties arise interact life. Martin Högbom Professor Structural Biochemistry, Wallenberg Scholar Head Department Biochemistry Biophysics Stockholm University. His focusses enzymology, particular catalysis Ribonucleotide Reductase, Methane Monooxygenase respiratory complexes. visiting professor Stanford University School Medicine 2018 Chemistry 2016. awarded European Medal Bio-Inorganic 2010, served president Young Academy Sweden during 2014–2015 elected member Royal Swedish Sciences 2020.

Language: Английский

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