Tag: 200-300

Application of the deep learning algorithm in nutrition research – using serum pyridoxal 5′-phosphate as an example was written by Ma, Chaoran;Chen, Qipin;Mitchell, Diane C.;Na, Muzi;Tucker, Katherine L.;Gao, Xiang. And the article was included in Nutrition Journal in 2022.COA of Formula: C8H10NO6P The following contents are mentioned in the article:

Abstract: Background: Multivariable linear regression (MLR) models were previously used to predict serum pyridoxal 5′-phosphate (PLP) concentration, the active coenzyme form of vitamin B6, but with low predictability. We developed a deep learning algorithm (DLA) to predict serum PLP based on dietary intake, dietary supplements, and other potential predictors. Methods: This cross-sectional anal. included 3778 participants aged ≥20 years in the National Health and Nutrition Examination Survey (NHANES) 2007-2010, with completed information on studied variables. Dietary intake and supplement use were assessed with two 24-h dietary recalls. We included potential predictors for serum PLP concentration in the models, including dietary intake and supplement use, sociodemog. variables (age, sex, race-ethnicity, income, and education), lifestyle variables (smoking status and phys. activity level), body mass index, medication use, blood pressure, blood lipids, glucose, and C-reactive protein. We used a 4-hidden-layer deep neural network to predict PLP concentration, with 3401 (90%) participants for training and 377 (10%) participants for test using random sampling. We obtained outputs after sending the features of the training set and conducting forward propagation. We then constructed a loss function based on the distances between outputs and labels and optimized it to find good parameters to fit the training set. We also developed a prediction model using MLR. Results: After training for 10⁵ steps with the Adam optimization method, the highest R² was 0.47 for the DLA and 0.18 for the MLR model in the test dataset. Similar results were observed in the sensitivity analyses after we excluded supplement-users or included only variables identified by stepwise regression models. Conclusions: DLA achieved superior performance in predicting serum PLP concentration, relative to the traditional MLR model, using a nationally representative sample. As preliminary data analyses, the current study shed light on the use of DLA to understand a modifiable lifestyle factor. This study involved multiple reactions and reactants, such as (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7COA of Formula: C8H10NO6P).

(4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7) belongs to pyridine derivatives. Pyridine is diamagnetic and has a diamagnetic susceptibility of −48.7 × 10−6 cm3·mol−1.The molecular electric dipole moment is 2.2 debyes. The standard enthalpy of formation is 100.2 kJ·mol−1 in the liquid phase and 140.4 kJ·mol−1 in the gas phase. Pyridine derivatives are also useful as small-molecule α-helix mimetics that inhibit protein-protein interactions, as well as functionally selective GABA ligands.COA of Formula: C8H10NO6P

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of the deep learning algorithm in nutrition research – using serum pyridoxal 5′-phosphate as an example was written by Ma, Chaoran;Chen, Qipin;Mitchell, Diane C.;Na, Muzi;Tucker, Katherine L.;Gao, Xiang. And the article was included in Nutrition Journal in 2022.Category: pyridine-derivatives The following contents are mentioned in the article:

Abstract: Background: Multivariable linear regression (MLR) models were previously used to predict serum pyridoxal 5′-phosphate (PLP) concentration, the active coenzyme form of vitamin B6, but with low predictability. We developed a deep learning algorithm (DLA) to predict serum PLP based on dietary intake, dietary supplements, and other potential predictors. Methods: This cross-sectional anal. included 3778 participants aged ≥20 years in the National Health and Nutrition Examination Survey (NHANES) 2007-2010, with completed information on studied variables. Dietary intake and supplement use were assessed with two 24-h dietary recalls. We included potential predictors for serum PLP concentration in the models, including dietary intake and supplement use, sociodemog. variables (age, sex, race-ethnicity, income, and education), lifestyle variables (smoking status and phys. activity level), body mass index, medication use, blood pressure, blood lipids, glucose, and C-reactive protein. We used a 4-hidden-layer deep neural network to predict PLP concentration, with 3401 (90%) participants for training and 377 (10%) participants for test using random sampling. We obtained outputs after sending the features of the training set and conducting forward propagation. We then constructed a loss function based on the distances between outputs and labels and optimized it to find good parameters to fit the training set. We also developed a prediction model using MLR. Results: After training for 10⁵ steps with the Adam optimization method, the highest R² was 0.47 for the DLA and 0.18 for the MLR model in the test dataset. Similar results were observed in the sensitivity analyses after we excluded supplement-users or included only variables identified by stepwise regression models. Conclusions: DLA achieved superior performance in predicting serum PLP concentration, relative to the traditional MLR model, using a nationally representative sample. As preliminary data analyses, the current study shed light on the use of DLA to understand a modifiable lifestyle factor. This study involved multiple reactions and reactants, such as (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7Category: pyridine-derivatives).

(4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7) belongs to pyridine derivatives. Pyridine’s the lone pair does not contribute to the aromatic system but importantly influences the chemical properties of pyridine, as it easily supports bond formation via an electrophilic attack. Pyridine derivatives are also useful as small-molecule α-helix mimetics that inhibit protein-protein interactions, as well as functionally selective GABA ligands.Category: pyridine-derivatives

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Bone-microarchitecture and bone-strength in a sample of adults with hypophosphatasia and a matched reference population assessed by HR-pQCT and impact microindentation was written by Hepp, Nicola;Folkestad, Lars;Moellebaek, Simone;Frederiksen, Anja Lisbeth;Duno, Morten;Joergensen, Niklas Rye;Hermann, Anne Pernille;Jensen, Jens-Erik Beck. And the article was included in Bone (New York, NY, United States) in 2022.Reference of 54-47-7 The following contents are mentioned in the article:

Hypophosphatasia (HPP) is an autosomal recessive or dominate disease affecting bone mineralization, and adults with HPP are in risk to develop metatarsal stress fractures and femoral pseudofractures. Given to the scarce data on the bone quality and its association to the fracture risk in adults with HPP, this study aimed to evaluate bone turnover, bone strength and structure in adults with HPP. In this cross-sectional study, we included 14 adults with genetically verified HPP and 14 sex-, age-, BMI-, and menopausal status-matched reference individuals. We analyzed bone turnover markers, and measured bone material strength index (BMSi) by impact microindentation. Bone geometry, volumetric d. and bone microarchitecture as well as failure load at the distal radius and tibia were evaluated using a second-generation high-resolution peripheral quant. computed tomog. system. Bone turnover markers did not differ between patients with HPP and reference individuals. BMSi did not differ between the groups (67.90 [63.75-76.00] vs 65.45 [58.43-69.55], p = 0.149). Parameters of bone geometry and volumetric d. did not differ between adults with HPP and the reference group. Patients with HPP had a tendency toward higher trabecular separation (0.664 [0.613-0.724] mm vs 0.620 [0.578-0.659] mm, p = 0.054) and inhomogeneity of trabecular network (0.253 [0.235-0.283] mm vs 0.229 [0.208-0.252] mm, p = 0.056) as well as lower trabecular bone volume fraction (18.8 [16.4-22.7] % vs 22.8 [20.6-24.7] %, p = 0.054) at the distal radius. In addition, compound heterozygous adults with HPP had a significantly higher cortical porosity at the distal radius than reference individuals (1.5 [0.9-2.2] % vs 0.7 [0.6-0.7] %, p = 0.041). BMSi is not reduced in adults with HPP. Increased cortical porosity may contribute to the occurrence of femoral pseudofractures in compound heterozygous adults with HPP. However, further studies investigating larger cohorts of adults with HPP using methods of bone histomorphometry are recommended to adequately assess the bone quality in adults with HPP. This study involved multiple reactions and reactants, such as (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7Reference of 54-47-7).

(4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7) belongs to pyridine derivatives. Pyridine’s the lone pair does not contribute to the aromatic system but importantly influences the chemical properties of pyridine, as it easily supports bond formation via an electrophilic attack. Pyridine derivatives are also useful as small-molecule α-helix mimetics that inhibit protein-protein interactions, as well as functionally selective GABA ligands.Reference of 54-47-7

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Association of markers of inflammation, the kynurenine pathway and B vitamins with age and mortality, and a signature of inflammaging was written by Dugue, Pierre-Antoine;Hodge, Allison M.;Ulvik, Arve;Ueland, Per M.;Midttun, Oeivind;Rinaldi, Sabina;MacInnis, Robert J.;Li, Sherly X.;Meyer, Klaus;Navionis, Anne-Sophie;Flicker, Leon;Severi, Gianluca;English, Dallas R.;Vineis, Paolo;Tell, Grethe S.;Southey, Melissa C.;Milne, Roger L.;Giles, Graham G.. And the article was included in Journals of Gerontology in 2022.SDS of cas: 54-47-7 The following contents are mentioned in the article:

Inflammation is a key feature of aging. We aimed to (i) investigate the association of 34 blood markers potentially involved in inflammatory processes with age and mortality and (ii) develop a signature of “inflammaging.” Methods: Thirty-four blood markers relating to inflammation, B vitamin status, and the kynurenine pathway were measured in 976 participants in the Melbourne Collaborative Cohort Study at baseline (median age = 59 years) and follow-up (median age = 70 years). Associations with age and mortality were assessed using linear and Cox regression, resp. A parsimonious signature of inflammaging was developed and its association with mortality was compared with 2 marker scores calculated across all markers associated with age and mortality, resp. The majority of markers (30/34) were associated with age, with stronger associations observed for neopterin, cystatin C, interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), several markers of the kynurenine pathway and derived indexes KTR (kynurenine/tryptophan ratio), PAr index (ratio of 4-pyridoxic acid and the sum of pyridoxal 5′-phosphate and pyridoxal), and HK:XA (3-hydroxykynurenine/xanthurenic acid ratio). Many markers (17/34) showed an association with mortality, in particular IL-6, neopterin, C-reactive protein, quinolinic acid, PAr index, and KTR. The inflammaging signature included 10 markers and was strongly associated with mortality (hazard ratio [HR] per SD = 1.40, 95% CI: 1.24-1.57, p = 2 x 10^-8), similar to scores based on all age-associated (HR = 1.38, 95% CI: 1.23-1.55, p = 4 x 10^-8) and mortality-associated markers (HR = 1.43, 95% CI: 1.28-1.60, p = 1 x 10^-10), resp. Strong evidence of replication of the inflammaging signature association with mortality was found in the Hordaland Health Study. Our study highlights the key role of the kynurenine pathway and vitamin B6 catabolism in aging, along with other well-established inflammation-related markers. A signature of inflammaging based on 10 markers was strongly associated with mortality. This study involved multiple reactions and reactants, such as (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7SDS of cas: 54-47-7).

(4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7) belongs to pyridine derivatives. The pyridine ring occurs in many important compounds, including agrochemicals, pharmaceuticals, and vitamins. Several pyridine derivatives play important roles in biological systems. While its biosynthesis is not fully understood, nicotinic acid (vitamin B3) occurs in some bacteria, fungi, and mammals.SDS of cas: 54-47-7

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Thiamine-dependent regulation of mammalian brain pyridoxal kinase in vitro and in vivo was written by Bunik, Victoria;Aleshin, Vasily;Nogues, Isabel;Kahne, Thilo;Parroni, Alessia;Contestabile, Roberto;Salvo, Martino Luigi;Graf, Anastasia;Tramonti, Angela. And the article was included in Journal of Neurochemistry in 2022.Product Details of 54-47-7 The following contents are mentioned in the article:

Vitamins B₁ (thiamine) and B₆ (pyridox (al/ine/amine)) are crucial for central nervous system (CNS) function and neurogenesis due to the coenzyme action of their phosphorylated derivatives in the brain metabolism of glucose and neurotransmitters. Here, the non-coenzyme action of thiamine on the major mammalian producers of pyridoxal-5′-phosphate (PLP), such as pyridoxal kinase (PdxK) and pyridoxine 5′-phosphate oxidase (PNPO), is characterized. Among the natural thiamine compounds, thiamine triphosphate (ThTP) is the best effector of recombinant human PdxK (hPdxK) in vitro, inhibiting hPdxK in the presence of Mg²⁺ but activating the Zn²⁺-dependent reaction. Inhibition of hPdxK by thiamine antagonists decreases from amprolium to pyrithiamine to oxythiamine, highlighting possible dysregulation of both the B₁– and B₆-dependent metabolism in the chem. models of thiamine deficiency. Compared with the canonical hPdxK, the D87H and V128I variants show a twofold increase in K_app of thiamine inhibition, and the V128I and H246Q variants show a fourfold and a twofold decreased K_app of thiamine diphosphate (ThDP), resp. Thiamine administration changes diurnal regulation of PdxK activity and phosphorylation at Ser213 and Ser285, expression of the PdxK-related circadian kinases/phosphatases in the rat brain, and electrocardiog. (ECG). In contrast to PdxK, PNPO is not affected by thiamine or its derivatives, either in vitro or in vivo. Dephosphorylation of the PdxK Ser285, potentially affecting mobility of the ATP-binding loop, inversely correlates with the enzyme activity. Dephosphorylation of the PdxK Ser213, which is far away from the active site, does not correlate with the activity. The correlations anal. suggests the PdxK Ser213 to be a target of kinase MAP2K1 and phosphatase Ppp1ca. Diurnal effects of thiamine administration on the metabolically linked ThDP- and PLP-dependent enzymes may support the brain homeostatic mechanisms and physiol. fitness. This study involved multiple reactions and reactants, such as (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7Product Details of 54-47-7).

(4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7) belongs to pyridine derivatives. Pyridine has a dipole moment and a weaker resonant stabilization than benzene (resonance energy 117 kJ·mol−1 in pyridine vs. 150 kJ·mol−1 in benzene). Pyridine, its benzo and pyridine-based compounds play diverse roles in organic chemistry. Pyridine-based materials are valued for their optical and physical properties as well as their medical potential. Product Details of 54-47-7

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Thiamine-dependent regulation of mammalian brain pyridoxal kinase in vitro and in vivo was written by Bunik, Victoria;Aleshin, Vasily;Nogues, Isabel;Kahne, Thilo;Parroni, Alessia;Contestabile, Roberto;Salvo, Martino Luigi;Graf, Anastasia;Tramonti, Angela. And the article was included in Journal of Neurochemistry in 2022.Category: pyridine-derivatives The following contents are mentioned in the article:

Vitamins B₁ (thiamine) and B₆ (pyridox (al/ine/amine)) are crucial for central nervous system (CNS) function and neurogenesis due to the coenzyme action of their phosphorylated derivatives in the brain metabolism of glucose and neurotransmitters. Here, the non-coenzyme action of thiamine on the major mammalian producers of pyridoxal-5′-phosphate (PLP), such as pyridoxal kinase (PdxK) and pyridoxine 5′-phosphate oxidase (PNPO), is characterized. Among the natural thiamine compounds, thiamine triphosphate (ThTP) is the best effector of recombinant human PdxK (hPdxK) in vitro, inhibiting hPdxK in the presence of Mg²⁺ but activating the Zn²⁺-dependent reaction. Inhibition of hPdxK by thiamine antagonists decreases from amprolium to pyrithiamine to oxythiamine, highlighting possible dysregulation of both the B₁– and B₆-dependent metabolism in the chem. models of thiamine deficiency. Compared with the canonical hPdxK, the D87H and V128I variants show a twofold increase in K_app of thiamine inhibition, and the V128I and H246Q variants show a fourfold and a twofold decreased K_app of thiamine diphosphate (ThDP), resp. Thiamine administration changes diurnal regulation of PdxK activity and phosphorylation at Ser213 and Ser285, expression of the PdxK-related circadian kinases/phosphatases in the rat brain, and electrocardiog. (ECG). In contrast to PdxK, PNPO is not affected by thiamine or its derivatives, either in vitro or in vivo. Dephosphorylation of the PdxK Ser285, potentially affecting mobility of the ATP-binding loop, inversely correlates with the enzyme activity. Dephosphorylation of the PdxK Ser213, which is far away from the active site, does not correlate with the activity. The correlations anal. suggests the PdxK Ser213 to be a target of kinase MAP2K1 and phosphatase Ppp1ca. Diurnal effects of thiamine administration on the metabolically linked ThDP- and PLP-dependent enzymes may support the brain homeostatic mechanisms and physiol. fitness. This study involved multiple reactions and reactants, such as (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7Category: pyridine-derivatives).

(4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7) belongs to pyridine derivatives. In contrast to benzene, Pyridine’s electron density is not evenly distributed over the ring, reflecting the negative inductive effect of the nitrogen atom. Halopyridines are particularly attractive synthetic building blocks in a variety of cross-coupling methods, including the Suzuki-Miyaura cross-coupling reaction.Category: pyridine-derivatives

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Common and novel metabolic pathways related ESTs were upregulated in three date palm cultivars to ameliorate drought stress was written by Alhajhoj, Mohammed Refdan;Munir, Muhammad;Sudhakar, Balakrishnan;Ali-Dinar, Hassan Muzzamil;Iqbal, Zafar. And the article was included in Scientific Reports in 2022.Synthetic Route of C8H10NO6P The following contents are mentioned in the article:

Date palm is an important staple crop in Saudi Arabia, and about 400 different date palm cultivars grown here, only 50-60 of them are used com. The most popular and com. consumed cultivars of these are Khalas, Reziz, and Sheshi, which are also widely cultivated across the country. Date palm is high water-demanding crop in oasis agriculture, with an inherent ability to tolerate drought stress. However, the mechanisms by which it tolerates drought stress, especially at the transcriptomic level, are still elusive. This study appraised the physiol. and mol. response of three com. date palm cultivars Khalas, Reziz, and Sheshi at two different field capacities (FC; 100% and 25%) levels. At 25% FC (drought stress), leaf relative water content, chlorophyll, photosynthesis, stomatal conductance, and transpiration were significantly reduced. However, leaf intercellular CO2 concentration and water use efficiency increased under drought stress. In comparison to cvs.Khalas and Reziz, date palm cv.Sheshi showed less tolerance to drought stress. A total of 1118 drought-responsive expressed sequence tags (ESTs) were sequenced, 345 from Khalas, 391 from Reziz, and 382 from Sheshi and subjected to functional characterization, gene ontol. classification, KEGG pathways elucidation, and enzyme codes dissemination. Three date palm cultivars deployed a multivariate approach to ameliorate drought stress by leveraging common and indigenous mol., cellular, biol., structural, transcriptional and reproductive mechanisms. Approx. 50% of the annotated ESTs were related to photosynthesis regulation, photosynthetic structure, signal transduction, auxin biosynthesis, osmoregulation, stomatal conductance, protein synthesis/turnover, active transport of solutes, and cell structure modulation. Along with the annotated ESTs, ca. 45% of ESTs were novel. Conclusively, the study provides novel clues and opens the myriads of genetic resources to understand the fine-tuned drought amelioration mechanisms in date palm. This study involved multiple reactions and reactants, such as (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7Synthetic Route of C8H10NO6P).

(4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7) belongs to pyridine derivatives. Pyridine has a dipole moment and a weaker resonant stabilization than benzene (resonance energy 117 kJ·mol−1 in pyridine vs. 150 kJ·mol−1 in benzene). Pyridine, its benzo and pyridine-based compounds play diverse roles in organic chemistry. Pyridine-based materials are valued for their optical and physical properties as well as their medical potential. Synthetic Route of C8H10NO6P

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

The identification and application of a robust ω-transaminase with high tolerance towards substrates and isopropylamine from a directed soil metagenome was written by Xie, Youyu;Wang, Jiguo;Yang, Lin;Wang, Wei;Liu, Qinghai;Wang, Hualei;Wei, Dongzhi. And the article was included in Catalysis Science & Technology in 2022.Application of 54-47-7 The following contents are mentioned in the article:

ω-Transaminase-mediated asym. amination of a ketone substrate has gained significant attention for its immense potential to synthesize chiral amine pharmaceuticals and precursors. However, few of these have been authentically applied in industry due to inherent limitations such as low catalytic efficiency, unfavorable equilibrium, and poor tolerance towards high concentrations of substrate and isopropylamine (IPA). In this study, by specially screening a metagenomic library from amidogen-enriched environments established to retrieve class III transaminases, a robust ω-transaminase, ATA1012, was identified that exhibited high industrial potential. First, it showed relative stability at 30-50 °C and even at 30 °C for 800 h with residual activity >50%, which greatly benefits a continuous industrial process operation. Second, it was capable of tolerating IPA concentrations as high as 2 M. IPA is one of the most industrially favored amine donors because it is inexpensive and achiral; however, it is not widely accepted by most ω-transaminases. Third, it also showed high substrate tolerance towards the target ketones 1-Boc-3-piperidone (2t) and 1-Boc-3-pyrrolidone (2s) at concentrations up to 750 mM, and 2 IPA equivalent were sufficient to efficiently shift the equilibrium to the desired production side with up to 100% conversion. After systematic optimization of the reaction parameters, including the substrate loading, reaction temperature, IPA dosage and pyridoxal-5′-phosphate (PLP) concentration in the amination process, up to 0.75 M 1-Boc-3-piperidone (2t) (150 g L-1) and 1-Boc-3-pyrrolidone (2s) (139 g L-1) were efficiently converted to the corresponding chiral amines with ee values of >99.9% in 12 h. The hectogram reaction process was readily scaled up, producing a green productive amination process for the efficient production of chiral amines. The mol. basis of the outstanding catalytic efficiency of ATA1012 was also elucidated by mol. docking and mol. dynamics anal. This study involved multiple reactions and reactants, such as (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7Application of 54-47-7).

(4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7) belongs to pyridine derivatives. Pyridine has a conjugated system of six π electrons that are delocalized over the ring. The molecule is planar and, thus, follows the Hückel criteria for aromatic systems. Halopyridines are particularly attractive synthetic building blocks in a variety of cross-coupling methods, including the Suzuki-Miyaura cross-coupling reaction.Application of 54-47-7

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Computational Analysis on the Allostery of Tryptophan Synthase: Relationship between α/β-Ligand Binding and Distal Domain Closure was written by Ito, Shingo;Yagi, Kiyoshi;Sugita, Yuji. And the article was included in Journal of Physical Chemistry B in 2022.Synthetic Route of C8H10NO6P The following contents are mentioned in the article:

Tryptophan synthase (TRPS) is a bifunctional enzyme consisting of α and β-subunits and catalyzes the last two steps of L-tryptophan (L-Trp) biosynthesis, namely, cleavage of 3-indole-D-glycerol-3′-phosphate (IGP) into indole and glyceraldehyde-3-phosphate (G3P) in the α-subunit, and a pyridoxal phosphate (PLP)-dependent reaction of indole and L-serine (L-Ser) to produce L-Trp in the β-subunit. Importantly, the IGP binding at the α-subunit affects the β-subunit conformation and its ligand-binding affinity, which, in turn, enhances the enzymic reaction at the α-subunit. The intersubunit communications in TRPS have been investigated extensively for decades because of the fundamental and pharmaceutical importance, while it is still difficult to answer how TRPS allostery is regulated at the at. detail. Here, we investigate the allosteric regulation of TRPS by all-atom classical mol. dynamics (MD) simulations and analyze the potential of mean-force (PMF) along conformational changes of the α- and β-subunits. The present simulation has revealed a widely opened conformation of the β-subunit, which provides a pathway for L-Ser to enter into the β-active site. The IGP binding closes the α-subunit and induces a wide opening of the β-subunit, thereby enhancing the binding affinity of L-Ser to the β-subunit. Structural analyses have identified critical hydrogen bonds (HBs) at the interface of the two subunits (αG181-βS178, αP57-βR175, etc.) and HBs between the β-subunit (βT110 – βH115) and a complex of PLP and L-Ser (an α-aminoacrylate intermediate). The former HBs regulate the allosteric, β-subunit opening, whereas the latter HBs are essential for closing the β-subunit in a later step. The proposed mechanism for how the interdomain communication in TRPS is realized with ligand bindings is consistent with the previous exptl. data, giving a general idea to interpret the allosteric regulations in multidomain proteins. This study involved multiple reactions and reactants, such as (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7Synthetic Route of C8H10NO6P).

(4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7) belongs to pyridine derivatives. The pyridine ring occurs in many important compounds, including agrochemicals, pharmaceuticals, and vitamins. Pyridine derivatives are also useful as small-molecule α-helix mimetics that inhibit protein-protein interactions, as well as functionally selective GABA ligands.Synthetic Route of C8H10NO6P

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Computational Analysis on the Allostery of Tryptophan Synthase: Relationship between α/β-Ligand Binding and Distal Domain Closure was written by Ito, Shingo;Yagi, Kiyoshi;Sugita, Yuji. And the article was included in Journal of Physical Chemistry B in 2022.Safety of (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate The following contents are mentioned in the article:

Tryptophan synthase (TRPS) is a bifunctional enzyme consisting of α and β-subunits and catalyzes the last two steps of L-tryptophan (L-Trp) biosynthesis, namely, cleavage of 3-indole-D-glycerol-3′-phosphate (IGP) into indole and glyceraldehyde-3-phosphate (G3P) in the α-subunit, and a pyridoxal phosphate (PLP)-dependent reaction of indole and L-serine (L-Ser) to produce L-Trp in the β-subunit. Importantly, the IGP binding at the α-subunit affects the β-subunit conformation and its ligand-binding affinity, which, in turn, enhances the enzymic reaction at the α-subunit. The intersubunit communications in TRPS have been investigated extensively for decades because of the fundamental and pharmaceutical importance, while it is still difficult to answer how TRPS allostery is regulated at the at. detail. Here, we investigate the allosteric regulation of TRPS by all-atom classical mol. dynamics (MD) simulations and analyze the potential of mean-force (PMF) along conformational changes of the α- and β-subunits. The present simulation has revealed a widely opened conformation of the β-subunit, which provides a pathway for L-Ser to enter into the β-active site. The IGP binding closes the α-subunit and induces a wide opening of the β-subunit, thereby enhancing the binding affinity of L-Ser to the β-subunit. Structural analyses have identified critical hydrogen bonds (HBs) at the interface of the two subunits (αG181-βS178, αP57-βR175, etc.) and HBs between the β-subunit (βT110 – βH115) and a complex of PLP and L-Ser (an α-aminoacrylate intermediate). The former HBs regulate the allosteric, β-subunit opening, whereas the latter HBs are essential for closing the β-subunit in a later step. The proposed mechanism for how the interdomain communication in TRPS is realized with ligand bindings is consistent with the previous exptl. data, giving a general idea to interpret the allosteric regulations in multidomain proteins. This study involved multiple reactions and reactants, such as (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7Safety of (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate).

(4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7) belongs to pyridine derivatives. In contrast to benzene, Pyridine’s electron density is not evenly distributed over the ring, reflecting the negative inductive effect of the nitrogen atom. Pyridine, its benzo and pyridine-based compounds play diverse roles in organic chemistry. Pyridine-based materials are valued for their optical and physical properties as well as their medical potential. Safety of (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem