Allostery can convert binding free energies into concerted domain motions in enzymes DOI Creative Commons
Nicole Stéphanie Galenkamp, Sarah Zernia,

Yulan B. Van Oppen

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 22, 2024

Abstract Enzymatic mechanisms are typically inferred from structural data. However, understanding enzymes require unravelling the intricate dynamic interplay between dynamics, conformational substates, and multiple protein structures. Here, we use single-molecule nanopore analysis to investigate catalytic changes of adenylate kinase (AK), an enzyme that catalyzes interconversion various adenosine phosphates (ATP, ADP, AMP). Kinetic validated by hidden Markov models unravels details domain motions during catalysis. Our findings reveal allosteric interactions ligands cofactor enable converting binding energies into directional two domains AK. These coordinated emerged control exact sequence ligand affinity for three different substrates, thereby guiding reactants along reaction coordinates. Interestingly, find about 10% show altered regulation affinities, indicating a subset folds in alternative catalytically active forms. Since molecules or proteins might be able selectively stabilize one folds, this observation suggests evolutionary path allostery enzymes. In AK, complex framework has likely prevent futile ATP/ADP hydrolysis regulate energy needs cell.

Язык: Английский

Heterologous Expression and Functional Analysis of Exiguobacterium Algin Lyase Gene by Pichia pastoris DOI Creative Commons

Wu HanWen,

Kai Hou, Yutong Jiang

и другие.

Fermentation, Год журнала: 2025, Номер 11(1), С. 34 - 34

Опубликована: Янв. 16, 2025

Algin is the most abundant substance in alga. Alginate lyase degrades algin and produces monosaccharides, disaccharides, oligosaccharides, which are widely used bioenergy, food, medicine, other fields. In this study, one Exiguobacterium strain isolated from rotten kelp exhibited a robust ability to degrade The sequencing of revealed presence three different types alginate lyase. Nevertheless, expression genes Escherichia coli lower activity compared that original strain. After codon optimization, gene with highest was successfully expressed Pichia pastoris produce recombinant EbAlg664. enzyme 5 L high-density fermentation reached 1306 U/mg protein, 3.9 times results enzymatic analysis optimal temperature pH range EbAlg664 were narrower Additionally, Cu2+ Co2+ enhanced activity, whereas Mg2+ Fe3+ inhibitory effects on study offers theoretical practical foundation for industrial-scale production engineered high activity.

Язык: Английский

Процитировано

0

Molecular Matchmakers: How ATP and Small Amphiphilic Molecules Fine-Tune FET Proteins Clusters DOI
Mrityunjoy Kar

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

Abstract FET (FUS-EWSR1-TAF15) family proteins inherently form mesoscale molecular assemblies, known as clusters, under physiological conditions at concentrations well below the threshold for phase separation. This study demonstrates that adenosine triphosphate (ATP), an amphiphilic molecule and essential cellular metabolite, modulates size of these sub-saturation clusters in a concentration-dependent manner. At low (1-2 mM), ATP acts crosslinker proteins, resulting larger clusters. moderate (5 decreases but stabilizes. high (10 cluster further diminishes. Other molecules, including common hydrotropes like sodium xylene sulfonate, toluene hexanediol, exhibit comparable effects on protein clustering. Notably, cannot be explained solely by hydrotropic or kosmotropic mechanisms; instead, they stem from non-specific interactions between small molecules. The intrinsic chemical properties molecules play crucial role regulating formation concentrations.

Язык: Английский

Процитировано

0

Magnesium: Der Schlüssel zur Langlebigkeit DOI
Uwe Gröber,

Klaus Kisters

Zeitschrift für Orthomolekulare Medizin, Год журнала: 2025, Номер 23(01), С. 22 - 29

Опубликована: Апрель 1, 2025

Процитировано

0

Metal-organic frameworks (MOF-74) show distinct bio-effects to nitrogen-fixing bacterium Azotobacter vinelandii DOI

Fangshi Liu,

Hongtao Wang, Ziqi Tang

и другие.

Journal of Hazardous Materials, Год журнала: 2025, Номер 494, С. 138779 - 138779

Опубликована: Май 29, 2025

Язык: Английский

Процитировано

0

Allostery can convert binding free energies into concerted domain motions in enzymes DOI Creative Commons
Nicole Stéphanie Galenkamp, Sarah Zernia,

Yulan B. Van Oppen

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 22, 2024

Abstract Enzymatic mechanisms are typically inferred from structural data. However, understanding enzymes require unravelling the intricate dynamic interplay between dynamics, conformational substates, and multiple protein structures. Here, we use single-molecule nanopore analysis to investigate catalytic changes of adenylate kinase (AK), an enzyme that catalyzes interconversion various adenosine phosphates (ATP, ADP, AMP). Kinetic validated by hidden Markov models unravels details domain motions during catalysis. Our findings reveal allosteric interactions ligands cofactor enable converting binding energies into directional two domains AK. These coordinated emerged control exact sequence ligand affinity for three different substrates, thereby guiding reactants along reaction coordinates. Interestingly, find about 10% show altered regulation affinities, indicating a subset folds in alternative catalytically active forms. Since molecules or proteins might be able selectively stabilize one folds, this observation suggests evolutionary path allostery enzymes. In AK, complex framework has likely prevent futile ATP/ADP hydrolysis regulate energy needs cell.

Язык: Английский

Процитировано

1