Harnessing lignocellulosic biomass: Insights into pre‐treatment strategies and hydrolytic enzyme production

Industrial Crops and Products, Journal Year: 2025, Volume and Issue: 229, P. 120986 - 120986

Published: April 16, 2025

Language: Английский

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Electrostatic potential as a reactivity scoring function in computer‐assisted enzyme engineering

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

Published: May 5, 2025

The high catalytic efficiency of enzymes is attained, in part, by their capacity to stabilize electrostatically the transition state chemical reaction. High‐throughput protocols for measuring this electrostatic contribution computer‐assisted enzyme design are limited. We present here an easy‐to‐compute metric that captures complementarity charge distribution substrate at state. demonstrate such a representative dataset glycoside hydrolases, large family responsible hydrolytic cleavage glycosidic bonds oligosaccharides, polysaccharides, and glycoconjugates. have implemented BindScan , computer‐based mutational analysis protocol assist protein engineering. predictive power with two mechanistically distinct hydrolases: Spodoptera frugiperda β‐glucosidase ( Sf βgly, operates via nucleophile catalysis) Bifidobacterium bifidum lacto‐ N ‐biosidase Bb LnbB, substrate‐assisted catalysis). correctly predicts sequence positions sensible modulation k cat / K M upon mutation from experimental benchmark 51 mutants βgly 77% classification identifies variants LnbB improved transglycosylation yields (up 32%). Based on potential ligand affinity calculations, as we propose rational strategy hydrolase synthesis added‐value new reactivity may contribute expanding range computational available engineering campaigns aimed optimizing relevant properties.

Language: Английский

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C-Ribosylating Enzymes in the (Bio)Synthesis of C-Nucleosides and C-Glycosylated Natural Products

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(24), P. 15910 - 15938

Published: Nov. 28, 2023

Small-molecule glycosides that exhibit a β-d-ribosyl residue linked to an aglycone via noncanonical C-glycosidic linkage are of great biological importance. They occur naturally in the C-nucleoside pseudouridine (Ψ), as well diverse class natural product C-ribosides involve broad variation structure and show interesting range functions. Many strong antimicrobial activity, so they relevant for development antibiotics. Ψ N1-methylated derivative thereof used replace uridine synthetic RNAs therapeutic applications, including mRNA vaccines against SARS-CoV-2 infections. The also serve inspirational lead structures medicinal chemistry develop new drug candidates. Recent evidence on C-β-riboside biosynthetic enzymes [pseudouridine synthases 4-(d-ribofuranosyl) aminobenzene synthases] reveals fascinating diversity active-site catalytic mechanisms install crucial aglycone. We here review context their pathways with particular focus reactions possible applications synthesis. A family coined by Ψ-5′-phosphate C-glycosidases involves surprising mechanistic plasticity formation C-β-ribosyl linkages. proposed underlying C-glycosidase-like reviewed here. reverse reaction C-glycosidase (a catabolic enzyme degradation pathway) is shown provide access analogues structural pentose nucleobase moieties. Enzyme cascade engineered vivo biosynthesis promising strategies scalable Multistep one-pot rearrangement into represents example synthesis at industrial-level productivity.

Language: Английский

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Activity-dependent glassy cell mechanics II: Nonthermal fluctuations under metabolic activity

Biophysical Journal, Journal Year: 2023, Volume and Issue: 122(22), P. 4395 - 4413

Published: Oct. 20, 2023

Language: Английский

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A Refined Nomenclature System to Better Discriminate Endo- and Exo-Type Fructanases and Glucanases

Biomolecules, Journal Year: 2024, Volume and Issue: 15(1), P. 11 - 11

Published: Dec. 25, 2024

Distinguishing between endo- and exo-type enzymes within the glycoside hydrolase (GH) classification presents significant challenges. Traditional methods, often based on endpoint activity measurements, do not capture full range of products generated, leading to inconsistencies in classification. Not all exo-acting fructanases glucanases produce monosaccharides (like fructose or glucose), while endo-acting solely higher-degree polymerization oligosaccharides. In practice, both enzyme types can yield a variety throughout reaction, complicating efforts. To address these challenges, we propose refined nomenclature system for GH enzymes, including glucanases, good practices initial product formation. This classifies into four categories each type: Fr, Fn, Fn,n+1 F1 fructanases, Gr, Gn, Gn,n+1 G1 their mode action (endo- exo-based) profiles. Our will advance structure–function research support production application fructan glucan oligosaccharides as prebiotics, priming agents, potential signaling molecules microbe–microbe plant–microbe interactions. Ultimately, this could benefit agronomy food industry, contributing health improvements.

Language: Английский

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Human O-GlcNAcase Uses a Preactivated Boat-skew Substrate Conformation for Catalysis. Evidence from X-ray Crystallography and QM/MM Metadynamics

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(20), P. 13672 - 13678

Published: Oct. 10, 2023

Human O-linked β-N-acetylglucosaminidase (hOGA) is one of the two enzymes involved in nuclear and cytoplasmic protein O-GlcNAcylation, an essential post-translational modification. The enzyme catalyzes hydrolysis GlcNAc-O-(Ser/Thr) glycosidic bonds via anchimeric assistance through 2-acetamido group GlcNAc sugar. However, conformational itinerary ring during catalysis remains unclear. Here we report crystal structure wild type hOGA complex with a nonhydrolyzable glycopeptide substrate elucidate full catalytic mechanism using QM/MM metadynamics. We show that can bind either chair- or boat-like conformation, but only latter catalytically competent, leading to reaction products 1,4B/1S3 → [4E]‡ 4C1 itineraries for first second steps, respectively. Our results reconcile previous experimental observations human bacterial OGA will aid development more effective inhibitors diseases associated impaired O-GlcNAcylation.

Language: Английский

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Functioning and mechanisms of PTMs in renal diseases

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 21, 2023

Post-translational modifications (PTMs) are crucial epigenetic mechanisms that regulate various cellular biological processes. The use of mass spectrometry (MS)-proteomics has led to the discovery numerous novel types protein PTMs, such as acetylation, crotonylation, 2-hydroxyisobutyrylation, β-hydroxybutyrylation, propionylation and butyrylation, succinylation, malonylation, lactylation, histone methylation. In this review, we specifically highlight molecular roles some non-histone PTMs in renal diseases, including diabetic kidney disease. exhibit diverse effects on which can be either protective or detrimental, depending specific type their respective targets. Different activate signaling pathways pathological conditions, could provide insights for studying developing potential therapeutic strategies diseases.

Language: Английский

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Borylated Monosaccharide 3-Boronic-3-deoxy-d-galactose: Detailed NMR Spectroscopic Characterisation, and Method for Spectroscopic Analysis of Anomeric and Boron Equilibria

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12396 - 12396

Published: Nov. 19, 2024

Drug leads with a high Fsp

Language: Английский

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In silicomodelling of the function of disease-related CAZymes

Essays in Biochemistry, Journal Year: 2023, Volume and Issue: 67(3), P. 355 - 372

Published: March 13, 2023

Abstract In silico modelling of proteins comprises a diversity computational tools aimed to obtain structural, electronic, and/or dynamic information about these biomolecules, capturing mechanistic details that are challenging experimental approaches, such as elusive enzyme-substrate complexes, short-lived intermediates, and reaction transition states (TS). The present article gives the reader insight on use in techniques understand complex catalytic mechanisms carbohydrate-active enzymes (CAZymes), along with underlying theory concepts important this field. We start by introducing significance carbohydrates nature process them, CAZymes, highlighting conformational flexibility their carbohydrate substrates. Three commonly used methods (classical molecular dynamics (MD), hybrid quantum mechanics/molecular mechanics (QM/MM), enhanced sampling techniques) described for nonexpert readers. Finally, we provide three examples application unravel disease-related CAZymes: β-galactocerebrosidase (GALC), responsible Krabbe disease; α-mannoside β-1,6-N-acetylglucosaminyltransferase V (MGAT5), involved cancer; O-fucosyltransferase 1 (POFUT1), several human diseases leukemia Dowling–Degos disease.

Language: Английский

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Computational modeling of protein–carbohydrate interactions: Current trends and future challenges

Advances in carbohydrate chemistry and biochemistry, Journal Year: 2023, Volume and Issue: unknown, P. 133 - 149

Published: Jan. 1, 2023

Language: Английский

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