Protecting the Achilles heel: three FolE_I-type GTP-cyclohydrolases needed for full growth of metal-resistant Cupriavidus metallidurans under a variety of conditions DOI Creative Commons

Vladislava Schulz,

Diana Galea,

Martin Herzberg

et al.

Journal of Bacteriology, Journal Year: 2024, Volume and Issue: 206(2)

Published: Jan. 16, 2024

ABSTRACT In Cupriavidus metallidurans and other bacteria, biosynthesis of the essential biochemical cofactor tetrahydrofolate (THF) initiates from guanosine triphosphate (GTP). This step is catalyzed by FolE_I-type GTP cyclohydrolases, which are either zinc-dependent FolE_IA-type or metal-promiscuous FolE_IB-type enzymes. As THF also for biosynthesis, synthesis form a cooperative cycle, may be influenced cellular homeostasis zinc metal cations. Metal-resistant C. harbors one two All three proteins were produced in Escherichia coli . FolE_IA was indeed dependent FolE_IB enzymes cyclohydrolases vitro , latter, example, functioning with iron, manganese, cobalt. Single double mutants deletions folE_I genes constructed to analyze contribution individual under various conditions. required presence cadmium, hydrogen peroxide, chelators, general starvation FolE_IB1 important when uptake impaired cells without importer ZupT (ZIP family) trimethoprim, an inhibitor biosynthesis. FolE_IB2 needed conditions low cobalt but high magnesium availability. Together, these data demonstrate that requires all allow efficient growth variety IMPORTANCE Tetrahydrofolate microbial biochemistry. “Achilles heel” metabolism has been exploited anti-metabolites antibiotics such as sulfonamide trimethoprim. Since (GTP) starts GTP, both compounds forms cycle. The first (FolEs) zinc- enzymes, so cycle several cations, especially zinc. metal-resistant bacterium needs FolEs grow environments cadmium content. Consequently, bacterial guarantee

Language: Английский

Multiscale architecture design of 3D printed biodegradable Zn-based porous scaffolds for immunomodulatory osteogenesis DOI Creative Commons
Shuang Li, Hongtao Yang, Xinhua Qu

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 11, 2024

Abstract Reconciling the dilemma between rapid degradation and overdose toxicity is challenging in biodegradable materials when shifting from bulk to porous materials. Here, we achieve significant bone ingrowth into Zn-based scaffolds with 90% porosity via osteoinmunomodulation. At microscale, an alloy incorporating 0.8 wt% Li employed create a eutectoid lamellar structure featuring LiZn 4 Zn phases. This microstructure optimally balances high strength immunomodulation effects. mesoscale, surface pattern nanoscale roughness facilitates filopodia formation macrophage spreading. macroscale, isotropic minimal G unit exhibits proper rate more uniform feature compared anisotropic BCC unit. In vivo, scaffold demonstrates heightened efficiency promoting polarization toward anti-inflammatory phenotype, subsequently leading significantly elevated osteogenic markers, increased collagen deposition, enhanced new formation. vitro, transcriptomic analysis reveals activation of JAK/STAT pathways macrophages up regulating expression Il-4 , Il-10 osteogenesis.

Language: Английский

Citations

25
Development of Platinum Complexes for Tumor Chemoimmunotherapy DOI
S. Jin, Yan Guo, Xiaoyong Wang

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(10)

Published: Jan. 3, 2024

Abstract Platinum complexes are potential antitumor drugs in chemotherapy. Their impact on tumor treatment could be greatly strengthened by combining with immunotherapy. Increasing evidences indicate that the activity of platinum is not limited to chemical killing effects, but also extends immunomodulatory actions. This review introduced general concept chemoimmunotherapy and summarized progress as chemoimmunotherapeutic agents recent years. developed into inducers immunogenic cell death, blockers immune checkpoint, regulators signaling pathway, modulators microenvironment, etc. The synergy between chemotherapeutic effects reinforces complexes, helps them circumvent drug resistance systemic toxicity. exploration for may create new opportunities revive discovery metal anticancer drugs.

Language: Английский

Citations

16
Metal Ion Signaling in Biomedicine DOI Creative Commons
Raphaël Rodriguez, Sebastian Müller, Ludovic Colombeau

et al.

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Complex multicellular organisms are composed of distinct tissues involving specialized cells that can perform specific functions, making such life forms possible. Species defined by their genomes, and differences between individuals within a given species directly result from variations in genetic codes. While alterations give rise to disease-causing acquisitions cell identities, it is now well-established biochemical imbalances also lead cellular dysfunction diseases. Specifically, nongenetic chemical events orchestrate metabolism transcriptional programs govern functional identity. Thus, signaling, which broadly defines the conversion extracellular signals into intracellular changes, contribute acquisition diseased states. Metal ions exhibit unique properties be exploited cell. For instance, metal maintain ionic balance cell, coordinate amino acid residues or nucleobases altering folding function biomolecules, catalyze reactions. metals essential signaling effectors normal physiology disease. Deciphering ion challenging endeavor illuminate pathways targeted for therapeutic intervention. Here, we review key processes where play roles describe how targeting has been instrumental dissecting biochemistry this led development effective strategies.

Language: Английский

Citations

2
Age-associated interplay between zinc deficiency and Golgi stress hinders microtubule-dependent cellular signaling and epigenetic control DOI
Sofia Brito, Hyojin Heo, Jinyoung Kim

et al.

Developmental Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

2
Disruption of Zinc Homeostasis by a Novel Platinum(IV)‐Terthiophene Complex for Antitumor Immunity DOI

Xuxian Su,

Bin Liu, Wenjin Wang

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(8)

Published: Dec. 22, 2022

Zinc homeostatic medicine is of great potential for cancer chemo-immunotherapy; however, there are few reports on antitumor compounds that can trigger Zn2+ -mediated immune responses. In this work, we developed a novel cyclometalated PtIV -terthiophene complex, Pt3, not only induces DNA damage and cellular metabolism dysregulation, but also disrupts zinc homeostasis as indicated by the abnormal transcriptional level regulatory proteins, excess accumulation in cytoplasm, down-regulation metallothioneins (MTs), which further caused redox imbalance. The simultaneous disruption response to Pt3 treatment activated gasdermin-D mediated pyroptosis accompanied cytoskeleton remodeling, thus releasing pro-inflammatory cytokines promote dendritic cell (DC) maturation T tumor-infiltration, eventually eliminating both primary distant tumors vivo. As far know, first metal complex regulate activate immunity.

Language: Английский

Citations

51
Zinc-Based Biodegradable Materials for Orthopaedic Internal Fixation DOI Creative Commons
Yang Liu,

Tianming Du,

Aike Qiao

et al.

Journal of Functional Biomaterials, Journal Year: 2022, Volume and Issue: 13(4), P. 164 - 164

Published: Sept. 26, 2022

Traditional inert materials used in internal fixation have caused many complications and generally require removal with secondary surgeries. Biodegradable materials, such as magnesium (Mg)-, iron (Fe)- zinc (Zn)-based alloys, open up a new pathway to address those issues. During the last decades, Mg-based alloys attracted much attention by researchers. However, issues an over-fast degradation rate release of hydrogen still need be overcome. Zn comparable mechanical properties traditional metal e.g., titanium (Ti), moderate rate, potentially serving good candidate for especially at load-bearing sites skeleton. Emerging Zn-based composites been developed recent years vitro vivo studies performed explore their biodegradability, property, biocompatibility order move towards ultimate goal clinical application fracture fixation. This article seeks offer review related research progress on biodegradable which may provide useful reference future targeting applications orthopedic

Language: Английский

Citations

42
The elements of life: A biocentric tour of the periodic table DOI

Kaleigh A. Remick,

John D. Helmann

Advances in microbial physiology/Advances in Microbial Physiology, Journal Year: 2023, Volume and Issue: unknown, P. 1 - 127

Published: Jan. 1, 2023

Language: Английский

Citations

39
An iron–sulfur cluster in the zinc-binding domain of the SARS-CoV-2 helicase modulates its RNA-binding and -unwinding activities DOI Creative Commons
Nunziata Maio, Md Kausar Raza, Yan Li

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(33)

Published: Aug. 8, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, uses an RNA-dependent RNA polymerase along with several accessory factors to replicate its genome and transcribe genes. Nonstructural protein (nsp) 13 is a helicase required for viral replication. Here, we found that nsp13 ligates iron, in addition zinc, when purified anoxically. Using inductively coupled plasma mass spectrometry, UV-visible absorption, EPR, Mössbauer spectroscopies, characterized as iron–sulfur (Fe–S) Fe 4 S cluster treble-clef metal-binding site zinc-binding domain. The Fe–S modulates both binding template unwinding activity. Exposure stable nitroxide TEMPOL oxidizes degrades drastically diminishes Thus, optimal function depends on labile potentially targetable COVID-19 treatment.

Language: Английский

Citations

27
NAC controls cotranslational N-terminal methionine excision in eukaryotes DOI
Martin Gamerdinger, Min Jia,

Renate Schloemer

et al.

Science, Journal Year: 2023, Volume and Issue: 380(6651), P. 1238 - 1243

Published: June 22, 2023

N-terminal methionine excision from newly synthesized proteins, catalyzed cotranslationally by aminopeptidases (METAPs), is an essential and universally conserved process that plays a key role in cell homeostasis protein biogenesis. However, how METAPs interact with ribosomes their cleavage specificity ensured unknown. We discovered eukaryotes the nascent polypeptide-associated complex (NAC) controls ribosome binding of METAP1. NAC recruits METAP1 using long, flexible tail provides platform for formation active at ribosomal tunnel exit. This mode interaction ensures efficient cytosolic whereas proteins targeted to endoplasmic reticulum are spared. Our results suggest broader mechanism access biogenesis factors translating controlled.

Language: Английский

Citations

23
Zein-Coated Zn Metal Particles-Incorporated Nanofibers: A Potent Fibrous Platform for Loading and Release of Zn Ions for Wound Healing Application DOI
Sita Shrestha, Bishnu Kumar Shrestha,

Felix Tettey-Engmann

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(37), P. 49197 - 49217

Published: Sept. 5, 2024

Metal particles incorporated into polymer matrices in various forms and geometries are attractive material platforms for promoting wound healing preventing infections. However, the fate of these metal their degraded products tissue environment still unknown, as both can produce cytotoxic effects promote unwanted reactions. In this study, we develop biodegradable fibrous biomaterials embedded with that have an immune activation functions. Initially, zinc (Zn) nanoparticles were modified zein (G), a protein derived from corn. The zein-coated (Z-G) then polycaprolactone (P) fibers at different weight ratios to create via electrospinning, which subsequently analyzed potential applications. We performed multimodal evaluations scaffolds, examining physicochemical properties such fiber morphology, mechanical strength, hydrophilicity, degradation, release ions (Zn

Language: Английский

Citations

8