- Possible Nonneurological Health Benefits of Ketogenic Diet: Review of Scientific Reports over the Past Decade. [Review]
- The ketogenic diet (KD) has been used since the 1920s as a therapy for drug-resistant epilepsy. Due to the beneficial effects of this diet on the nervous system and the proposed multifaceted effects of ketones on health and disease, researchers have evaluated its use in other nonneurological conditions. The objective of this review was to analyze the most recent papers, which is why meta-analyses…
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- Modulation of Dyslipidemia Markers Apo B/Apo A and Triglycerides/HDL-Cholesterol Ratios by Low-Carbohydrate High-Fat Diet in a Rat Model of Metabolic Syndrome. [Journal Article]
- Metabolic syndrome (MetS) risks cardiovascular diseases due to its associated Dyslipidemia. It is proposed that a low-carbohydrate, high-fat (LCHF) diet positively ameliorates the MetS and reverses insulin resistance. Therefore, we aimed to investigate the protecting effect of the LCHF diet on MetS-associated Dyslipidemia in an experimental animal model. Forty male Sprague-Dawley rats were divide…
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- Structural Determinants of Sugar Alcohol Biosynthesis in Plants: The Crystal Structures of Mannose-6-Phosphate and Aldose-6-Phosphate Reductases. [Journal Article]
- Sugar alcohols are major photosynthetic products in plant species from the Apiaceae and Plantaginaceae families. Mannose-6-phosphate reductase (Man6PRase) and aldose-6-phosphate reductase (Ald6PRase) are key enzymes for synthesizing mannitol and glucitol in celery (Apium graveolens) and peach (Prunus persica), respectively. In this work, we report the first crystal structures of dimeric plant ald…
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- Structural studies of codeinone reductase reveal novel insights into aldo-keto reductase function in benzylisoquinoline alkaloid biosynthesis. [Journal Article]
- Benzylisoquinoline alkaloids (BIAs) are a class of specialized metabolites with a diverse range of chemical structures and physiological effects. Codeine and morphine are two closely related BIAs with particularly useful analgesic properties. The aldo-keto reductase (AKR) codeinone reductase (COR) catalyzes the final and penultimate steps in the biosynthesis of codeine and morphine, respectively,…
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- Synthesis and Bioactivities of Marine Pyran-Isoindolone Derivatives as Potential Antithrombotic Agents. [Journal Article]
- 2,5-Bis-[8-(4,8-dimethyl-nona-3,7-dienyl)-5,7-dihydroxy-8-methyl-3-keto-1,2,7,8-teraahydro-6H-pyran[a]isoindol-2-yl]-pentanoic acid (FGFC1) is a marine pyran-isoindolone derivative isolated from a rare marine microorganism Stachybotrys longispora FG216, which showed moderate antithrombotic(fibrinolytic) activity. To further enhance its antithrombotic effect, a series of new FGFC1 derivatives (F1-…
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- Rare-Earth Metal Complexes of the Antibacterial Drug Oxolinic Acid: Synthesis, Characterization, DNA/Protein Binding and Cytotoxicity Studies. [Journal Article]
- "Drug repositioning" is a current trend which proved useful in the search for new applications for existing, failed, no longer in use or abandoned drugs, particularly when addressing issues such as bacterial or cancer cells resistance to current therapeutic approaches. In this context, six new complexes of the first-generation quinolone oxolinic acid with rare-earth metal cations (Y3+, La3+, Sm3+…
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- Structural and mechanistic insights into 5-lipoxygenase inhibition by natural products. [Journal Article]
- Leukotrienes (LT) are lipid mediators of the inflammatory response that are linked to asthma and atherosclerosis. LT biosynthesis is initiated by 5-lipoxygenase (5-LOX) with the assistance of the substrate-binding 5-LOX-activating protein at the nuclear membrane. Here, we contrast the structural and functional consequences of the binding of two natural product inhibitors of 5-LOX. The redox-type …
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- Structure-function study of AKR4C14, an aldo-keto reductase from Thai jasmine rice (Oryza sativa L. ssp. indica cv. KDML105). [Journal Article]Acta Crystallogr D Struct Biol. 2020 May 01; 76(Pt 5):472-483.AC
- Aldo-keto reductases (AKRs) are NADPH/NADP+-dependent oxidoreductase enzymes that metabolize an aldehyde/ketone to the corresponding alcohol. AKR4C14 from rice exhibits a much higher efficiency in metabolizing malondialdehyde (MDA) than do the Arabidopsis enzymes AKR4C8 and AKR4C9, despite sharing greater than 60% amino-acid sequence identity. This study confirms the role of rice AKR4C14 in the d…
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- Production, purification and physicochemical characterization of D-xylose/glucose isomerase from Escherichia coli strain BL21. [Journal Article]
- Cell lysate of Escherichia coli strain BL21 showed significant D-glucose isomerase activity. The rate of glucose conversion was increased up to 40% when cells were induced with 1% D-xylose. E. coli BL21 xylose isomerase (ECXI-BL21) was purified to homogeneity, up to 1.9-fold with overall 10.88% enzyme yield by heat shock, salting out and electro-elution. The molecular mass of ECXI-BL21 was estima…
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- Propagation of the Allosteric Signal in Phosphofructokinase from Bacillus stearothermophilus Examined by Methyl-Transverse Relaxation-Optimized Spectroscopy Nuclear Magnetic Resonance. [Journal Article]Biochemistry. 2019 12 31; 58(52):5294-5304.B
- Phosphofructokinase from Bacillus stearothermophilus (BsPFK) is a 136 kDa homotetromeric enzyme. Binding of the substrate, fructose 6-phosphate (Fru-6-P), is allosterically regulated by the K-type inhibitor phosphoenolpyruvate (PEP). The allosteric coupling between the substrate and inhibitor is quantified by a standard coupling free energy that defines an equilibrium with the Fru-6-P-bound and P…
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- Structure and Chemical Reaction Mechanism of LigU, an Enzyme That Catalyzes an Allylic Isomerization in the Bacterial Degradation of Lignin. [Journal Article]Biochemistry. 2019 08 20; 58(33):3494-3503.B
- LigU from Novosphingobium sp. strain KA1 catalyzes the isomerization of (4E)-oxalomesaconate (OMA) to (3Z)-2-keto-4-carboxy-3-hexenedioate (KCH) as part of the protocatechuate (PCA) 4,5-cleavage pathway during the degradation of lignin. The three-dimensional structure of the apo form of the wild-type enzyme was determined by X-ray crystallography, and the structure of the K66M mutant enzyme was d…
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- Free enzyme dynamics of CmaA3 and CmaA2 cyclopropane mycolic acid synthases from Mycobacterium tuberculosis: Insights into residues with potential significance in cyclopropanation. [Journal Article]
- Mycolic acids are long chain alpha-alkyl beta-hydroxy fatty acids that are major constituents of the cell wall of Mycobacterium tuberculosis. M. tuberculosis produces three main types of mycolic acids, alpha mycolic acids and keto and methoxy mycolic acids. Cycloproponated mycolic acids make the cell wall less permeable, contribute to antibiotic resistance and host immunomodulation and protect fr…
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- Transcriptional profiling of PPARα-/- and CREB3L3-/- livers reveals disparate regulation of hepatoproliferative and metabolic functions of PPARα. [Journal Article]
- CONCLUSIONS: These data indicate that CREB3L3 ablation uncouples the hepatoproliferative and lipid metabolic effects of PPARα. Overall, except for the shared regulation of a very limited number of genes, the roles of PPARα and CREB3L3 in hepatic lipid metabolism are clearly distinct and are highly dependent on dietary status.
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- Crystal structure and kinetic analyses of a hexameric form of (S)-3-hydroxybutyryl-CoA dehydrogenase from Clostridium acetobutylicum. [Journal Article]
- (S)-3-Hydroxybutyryl-CoA dehydrogenase (HBD) has been gaining increased attention recently as it is a key enzyme in the enantiomeric formation of (S)-3-hydroxybutyryl-CoA [(S)-3HB-CoA]. It converts acetoacetyl-CoA to (S)-3HB-CoA in the synthetic metabolic pathway. (S)-3HB-CoA is further modified to form (S)-3-hydroxybutyrate, which is a source of biodegradable polymers. During the course of a stu…
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- Crystal structure of yeast xylose reductase in complex with a novel NADP-DTT adduct provides insights into substrate recognition and catalysis. [Journal Article]
- Aldose reductases (ARs) belonging to the aldo-keto reductase (AKR) superfamily catalyze the conversion of carbonyl substrates into their respective alcohols. Here we report the crystal structures of the yeast Debaryomyces nepalensis xylose reductase (DnXR, AKR2B10) in the apo form and as a ternary complex with a novel NADP-DTT adduct. Xylose reductase, a key enzyme in the conversion of xylose to …
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- Identification, functional characterization, and crystal structure determination of bacterial levoglucosan dehydrogenase. [Journal Article]
- Levoglucosan is the 1,6-anhydrosugar of d-glucose formed by pyrolysis of glucans and is found in the environment and industrial waste. Two types of microbial levoglucosan metabolic pathways are known. Although the eukaryotic pathway involving levoglucosan kinase has been well-studied, the bacterial pathway involving levoglucosan dehydrogenase (LGDH) has not been well-investigated. Here, we identi…
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- Structures of Zymomonas 2-Keto-3-Deoxy-6-Phosphogluconate Aldolase with and without a Substrate Analog at the Phosphate-Binding Loop. [Journal Article]
- 2-Keto-3-deoxy-6-phosphogluconate (KDPG) aldolase, which catalyzes aldol cleavage and condensation reactions, has two distinct substrate-binding sites. The substrate-binding mode at the catalytic site and Schiff-base formation have been well studied. However, structural information on the phosphate-binding loop (P-loop) is limited. Zymomonas mobilis KDPG aldolase is one of the aldolases with a wi…
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- Structural, Biochemical, and Evolutionary Characterizations of Glyoxylate/Hydroxypyruvate Reductases Show Their Division into Two Distinct Subfamilies. [Journal Article]
- The d-2-hydroxyacid dehydrogenase (2HADH) family illustrates a complex evolutionary history with multiple lateral gene transfers and gene duplications and losses. As a result, the exact functional annotation of individual members can be extrapolated to a very limited extent. Here, we revise the previous simplified view on the classification of the 2HADH family; specifically, we show that the prev…
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- Thermal degradation kinetics of all-trans and cis-carotenoids in a light-induced model system. [Journal Article]
- Thermal degradation kinetics of lutein, zeaxanthin, β-cryptoxanthin, β-carotene was studied at 25, 35, and 45°C in a model system. Qualitative and quantitative analyses of all-trans- and cis-carotenoids were conducted using HPLC-DAD-MS technologies. Kinetic and thermodynamic parameters were calculated by non-linear regression. A total of 29 geometrical isomers and four oxidation products were det…
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- Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage. [Journal Article]
- Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M) as a synthetic polymer t…
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- Structure and characterization of a NAD(P)H-dependent carbonyl reductase from Pseudomonas aeruginosa PAO1. [Journal Article]FEBS Lett. 2017 06; 591(12):1785-1797.FL
- To investigate the function of the pa4079 gene from the opportunistic pathogen Pseudomonas aeruginosa PAO1, we determined its crystal structure and confirmed it to be a NAD(P)-dependent short-chain dehydrogenase/reductase. Structural similarity and activity for a broad range of substrates indicate that PA4079 functions as a carbonyl reductase. Comparison of apo- and holo-PA4079 shows that NADP st…
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- Structure-Based Engineering of an Artificially Generated NADP+-Dependent d-Amino Acid Dehydrogenase. [Journal Article]
- A stable NADP+-dependent d-amino acid dehydrogenase (DAADH) was recently created from Ureibacillus thermosphaericusmeso-diaminopimelate dehydrogenase through site-directed mutagenesis. To produce a novel DAADH mutant with different substrate specificity, the crystal structure of apo-DAADH was determined at a resolution of 1.78 Å, and the amino acid residues responsible for the substrate specifici…
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- A comparative structural analysis reveals distinctive features of co-factor binding and substrate specificity in plant aldo-keto reductases. [Journal Article]Biochem Biophys Res Commun. 2016 Jun 10; 474(4):696-701.BB
- Plant aldo-keto reductases of the AKR4C subfamily play key roles during stress and are attractive targets for developing stress-tolerant crops. However, these AKR4Cs show little to no activity with previously-envisioned sugar substrates. We hypothesized a structural basis for the distinctive cofactor binding and substrate specificity of these plant enzymes. To test this, we solved the crystal str…
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- Crystal Structures of Apo and Liganded 4-Oxalocrotonate Decarboxylase Uncover a Structural Basis for the Metal-Assisted Decarboxylation of a Vinylogous β-Keto Acid. [Journal Article]
- The enzymes in the catechol meta-fission pathway have been studied for more than 50 years in several species of bacteria capable of degrading a number of aromatic compounds. In a related pathway, naphthalene, a toxic polycyclic aromatic hydrocarbon, is fully degraded to intermediates of the tricarboxylic acid cycle by the soil bacteria Pseudomonas putida G7. In this organism, the 83 kb NAH7 plasm…
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- B-factor Analysis and Conformational Rearrangement of Aldose Reductase. [Journal Article]
- The NADPH-dependent reduction of glucose reaction that is catalyzed by Aldose Reductase (AR) follows a sequential ordered kinetic mechanism in which the co-factor NADPH binds to the enzyme prior to the aldehyde substrate. The kinetic/structural experiments have found a conformational change involving a hinge-like movement of a surface loop (residues 213-224) which is anticipated to take place upo…
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- High-resolution structures of mutants of residues that affect access to the ligand-binding cavity of human lipocalin-type prostaglandin D synthase. [Journal Article]
- Lipocalin-type prostaglandin D synthase (L-PGDS) catalyzes the isomerization of the 9,11-endoperoxide group of PGH2 (prostaglandin H2) to produce PGD2 (prostaglandin D2) with 9-hydroxy and 11-keto groups. The product of the reaction, PGD2, is the precursor of several metabolites involved in many regulatory events. L-PGDS, the first member of the important lipocalin family to be recognized as an e…
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- The first crystal structure of NAD-dependent 3-dehydro-2-deoxy-D-gluconate dehydrogenase from Thermus thermophilus HB8. [Journal Article]
- 2-Keto-3-deoxygluconate (KDG) is one of the important intermediates in pectin metabolism. An enzyme involved in this pathway, 3-dehydro-3-deoxy-D-gluconate 5-dehydrogenase (DDGDH), has been identified which converts 2,5-diketo-3-deoxygluconate to KDG. The enzyme is a member of the short-chain dehydrogenase (SDR) family. To gain insight into the function of this enzyme at the molecular level, the …
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- Structures of Saccharomyces cerevisiae D-arabinose dehydrogenase Ara1 and its complex with NADPH: implications for cofactor-assisted substrate recognition. [Journal Article]
- The primary role of yeast Ara1, previously mis-annotated as a D-arabinose dehydrogenase, is to catalyze the reduction of a variety of toxic α,β-dicarbonyl compounds using NADPH as a cofactor at physiological pH levels. Here, crystal structures of Ara1 in apo and NADPH-complexed forms are presented at 2.10 and 2.00 Å resolution, respectively. Ara1 exists as a homodimer, each subunit of which adopt…
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- Activation of an innate immune response in the schistosome-transmitting snail Biomphalaria glabrata by specific bacterial PAMPs. [Journal Article]
- Injection of crude lipopolysaccharide (LPS) from Escherichia coli into the hemocoel of Biomphalaria glabrata stimulates cell proliferation in the amebocyte-producing organ (APO). However, it is not known if mitogenic activity resides in the lipid A or O-polysaccharide component of LPS. Moreover, the possible role of substances that commonly contaminate crude LPS and that are known to stimulate in…
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- Structure of conjugated polyketone reductase from Candida parapsilosis IFO 0708 reveals conformational changes for substrate recognition upon NADPH binding. [Journal Article]
- Conjugated polyketone reductase C2 (CPR-C2) from Candida parapsilosis IFO 0708, identified as a nicotinamide adenine dinucleotide phosphate (NADPH)-dependent ketopantoyl lactone reductase, belongs to the aldo-keto reductase superfamily. This enzyme reduces ketopantoyl lactone to D-pantoyl lactone in a strictly stereospecific manner. To elucidate the structural basis of the substrate specificity, …
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