Falcao, Fatima’s team published research in Acta Medica Portuguesa in 2019 | 58-97-9

Acta Medica Portuguesa published new progress about 58-97-9. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, SDS of cas: 58-97-9.

Falcao, Fatima; Lopes, Carla; Viegas, Erica; Perez, Rita; Aldir, Isabel; Farinha, Helena; Carvalho, Antonio; Mirco, Ana; Marques, Susana; Costa, Tiago Bana E.; Miranda, Ana Claudia; Lebre, Luis; Peixe, Paula; Chagas, Cristina; Mansinho, Kamal; Correia, Jose Manuel published the artcile< Experience of a Portuguese center: effectiveness of direct-acting antiviral therapy for hepatitis C>, SDS of cas: 58-97-9, the main research area is Antiviral Agents/therapeutic use; Hepacivirus/drug effects; Hepatitis C/drug therapy; Portugal.

Introduction: In late 2014, Portugal implemented a national program for the treatment of patients with chronic hepatitis C with directacting antiviral agents. This program has made Portugal one of the first European countries to implement a structured measure of treatment to eliminate this serious public health problem. The aim of this study was to assess the effectiveness of direct-acting antiviral therapy in the treatment of patients with chronic hepatitis C virus infection. Material and Methods: A retrospective observational study was conducted at Centro Hospitalar de Lisboa Ocidental on the national online platform from Dec. 2014 until Feb. 2017 and included patients with hepatitis C virus infection who underwent treatment. The primary endpoint was sustained virol. response at least 12 wk post treatment. Data was analyzed with the SPSS 17.0 program. Results: During the study period, 820 patients completed therapy and achieved sufficient follow-up time to assess sustained virol. response with an overall response rate of 97.2% (n = 797) and a response rate of 98.0%, 99.5%, 90.9%, 95.1% and 94.2% for genotypes 1a, 1b, 2, 3 and 4, resp. Data suggested that advanced fibrosis (F3/F4), human immunodeficiency virus co-infection and treatment failure with interferon and ribavirin were not neg. related with sustained virol. response in our population. Most patients (80.1%) completed treatment with ledipasvir/sofosbuvir ± ribavirin. The most common adverse events were fatigue and insomnia followed by headache and weight loss. Discussion: Patients predominantly had genotype 1 infection which correlates with HCV distribution in Europe, but we found a major proportion in genotype 4 which can be explained by immigration from African countries. Our patients’ ages ranging from 22 to 90 years, reflected a new approach with no upper age limit. Direct-acting antivirals regimens resulted in remarkably high SVR rates compared to interferon-based regimens, which were consistent with clin. trials data. Conclusion: Our data showed that direct-acting antiviral-based regimens are safe and have a high success rate in the treatment of patients with hepatitis C virus infection in a real-world setting.

Acta Medica Portuguesa published new progress about 58-97-9. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, SDS of cas: 58-97-9.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Ryu, Incheol’s team published research in Journal of Biological Chemistry in 2019-05-10 | 58-97-9

Journal of Biological Chemistry published new progress about 3′-Untranslated region Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Product Details of C9H13N2O9P.

Ryu, Incheol; Kim, Yoon Ki published the artcile< AU-rich element-mediated mRNA decay via the butyrate response factor 1 controls cellular levels of polyadenylated replication-dependent histone mRNAs>, Product Details of C9H13N2O9P, the main research area is mRNA decay AU rich element BRF1 polyadenylated replication histone; ARE-mediated mRNA decay; ELAV like RNA binding protein 1 (ELAVL1); Hu antigen R (HuR); RNA; RNA degradation; RNA metabolism; RNA turnover; RNA-protein interaction; ZFP36 ring finger protein like 1 (ZFP36L1); butyrate response factor 1 (BRF1); histone mRNA biogenesis; mRNA stability; polyadenylation; posttranscriptional regulation; replication-dependent histone mRNA.

Replication-dependent histone (RDH) mRNAs have a nonpolyadenylated 3′-UTR that ends in a highly conserved stem-loop structure. Nonetheless, a subset of RDH mRNAs has a poly(A) tail under physiol. conditions. The biol. meaning of poly(A)-containing (+) RDH mRNAs and details of their biosynthesis remain elusive. Here, using HeLa cells and Western blotting, qRT-PCR, and biotinylated RNA pulldown assays, we show that poly(A)+ RDH mRNAs are post-transcriptionally regulated via adenylate- and uridylate-rich element-mediated mRNA decay (AMD). We observed that the rapid degradation of poly(A)+ RDH mRNA is driven by butyrate response factor 1 (BRF1; also known as ZFP36 ring finger protein-like 1) under normal conditions. Conversely, cellular stresses such as UV C irradiation promoted BRF1 degradation, increased the association of Hu antigen R (HuR; also known as ELAV-like RNA-binding protein 1) with the 3′-UTR of poly(A)+ RDH mRNAs, and eventually stabilized the poly(A)+ RDH mRNAs. Collectively, our results provide evidence that AMD surveils poly(A)+ RDH mRNAs via BRF1-mediated degradation under physiol. conditions.

Journal of Biological Chemistry published new progress about 3′-Untranslated region Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Product Details of C9H13N2O9P.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Nardelli, Silvia’s team published research in World journal of gastroenterology in 2019-12-28 | 58-97-9

World journal of gastroenterology published new progress about 58-97-9. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Synthetic Route of 58-97-9.

Nardelli, Silvia; Riggio, Oliviero; Rosati, Davide; Gioia, Stefania; Farcomeni, Alessio; Ridola, Lorenzo published the artcile< Hepatitis C virus eradication with directly acting antivirals improves health-related quality of life and psychological symptoms.>, Synthetic Route of 58-97-9, the main research area is Alexithymia; Depression; Directly acting antivirals; Health related quality of life; Hepatitis C virus; State and trait anxiety.

BACKGROUND: Alterations in health-related quality of life (HRQoL) and neuropsychological disorders were described in the hepatitis C virus (HCV) patients. Although several studies investigated the modifications of HRQoL after HCV eradication, no data exists on the modifications of neuropsychological symptoms. AIM: To investigate the effect of directly acting antivirals (DAAs) treatment on HRQoL and neuropsychological symptoms. METHODS: Thirty nine patients with HCV infection underwent a neuropsychological assessment, including Zung-Self Depression-Rating-Scale, Spielberg State-Trait Anxiety Inventory Y1-Y2 and the Toronto-Alexithymia Scale-20 items before and after DAAs treatment. HRQoL was detected by Short-Form-36 (SF-36). RESULTS: All HRQoL domains, but role limitation physical and bodily pain, significantly improved after treatment. Interestingly, after DAAs treatment, all domains of HRQoL returned similar to those of controls. Each neuropsychological test significantly improved after HCV eradication. A significant correlation was observed among each psychological test and the summary components of SF-36. At multiple linear regression analysis including each psychological test as possible covariates, Zung-Self Depression Rating Scale (Zung-SDS) score was independently and significantly related to summary components of the SF-36 in the basal state and the difference between Zung-SDS score before and after treatment was the only variable significantly and independently related to the modification of HRQoL induced by the treatment. CONCLUSION: Neuropsychological symptoms strongly influenced HRQoL in HCV patients and there was a significant improvement of neuropsychological tests and HRQoL after DAAs treatment.

World journal of gastroenterology published new progress about 58-97-9. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Synthetic Route of 58-97-9.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

El-Baraky, Iman A’s team published research in Clinics and Research in Hepatology and Gastroenterology in 2021-09-30 | 58-97-9

Clinics and Research in Hepatology and Gastroenterology published new progress about Geometric phase. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Formula: C9H13N2O9P.

El-Baraky, Iman A.; Abbassi, Maggie M.; Ebeid, Fatma S.; Hassany, Mohamed; Sabry, Nirmeen A.; El-Sayed, Manal H. published the artcile< Beta-thalassemia major alters sofosbuvir/ledipasvir exposure in Hepatitis C virus infected adolescent patients>, Formula: C9H13N2O9P, the main research area is beta thalassemia major sofosbuvir ledipasvir Hepatitis C virus; Hepatitis C virus; Ledipasvir; Pharmacokinetics; Sofosbuvir; Thalassemia.

Hepatitis C virus (HCV) infected adolescents with beta-thalassemia major (BTM) are considered a potential population for HCV micro-elimination model development where BTM may neg. impact the pharmacokinetic exposure parameters of sofosbuvir/ledipasvir (SOF/LED).The study aimed at studying the effect of BTM on SOF/LED and SOF metabolite (GS-331007) pharmacokinetics.A prospective, controlled study recruiting BTM and control HCV infected adolescents (Clinicaltrials.gov identifier-NCT04353986). Pharmacokinetic exposure to GS-331007 and LED was the primary pharmacokinetic outcome. No-effect boundaries were set to 90confidence interval (CI) of exposure geometric mean ratio (GMR) within 70-143. Dose suitability was based on the 90CI of exposure GMR within 50-200compared to adults. The percentage of patients achieving sustained virol. response 12 wk post-treatment (SVR12) was the primary efficacy endpoint.Thirteen patients were enrolled per study group. All patients were included in the pharmacokinetic anal. (n=26). BTM patients showed lower GS-331007 and LED exposure that could, resp., be as low as 45.4and 36.1compared to their control group. GS-331007 exposure in BTM patients was nearly half (56.8, 90CI 45.3-71.2) that observed in adults. Despite that low drug exposure in 46.2of BTM patients may alert dose unsuitability, they achieved SVR12. Moreover, patients with total bilirubin ≥1.93 mg/dL were predicted to have low GS-331007 exposure (0.913 receiver operating characteristic area under the curve with sensitivity and specificity >80).The identified systematically lower drug exposure in BTM patients might partially explain relapses or treatment failures among BTM patients reported in other studies. BTM may be a hurdle towards implementing HCV micro-elimination model that may necessitate dose-adjustment.

Clinics and Research in Hepatology and Gastroenterology published new progress about Geometric phase. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Formula: C9H13N2O9P.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Behairy, Behairy E’s team published research in Journal of Pediatrics (New York, NY, United States) in 2020-04-30 | 58-97-9

Journal of Pediatrics (New York, NY, United States) published new progress about Antiviral agents. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Computed Properties of 58-97-9.

Behairy, Behairy E.; El-Araby, Hanaa A.; El-Guindi, Mohamed A.; Basiouny, Hosam-Eldin M.; Fouad, Ola A.; Ayoub, Bassam A.; Marei, Ayman M.; Sira, Mostafa M. published the artcile< Safety and Efficacy of 8 Weeks Ledipasvir/Sofosbuvir for Chronic Hepatitis C Genotype 4 in Children Aged 4-10 Years>, Computed Properties of 58-97-9, the main research area is ledipasvir sofosbuvir antiviral agent hepatitis C virus infection; children; direct-acting antiviral drugs; efficacy; hepatitis C virus; ledipasvir; safety; sofosbuvir.

To evaluate the safety and efficacy of shortened 8-wk regimen of ledipasvir/sofosbuvir (LED/SOF) combination therapy in treatment-naive children without cirrhosis aged 4-10 years of age with chronic hepatitis C virus (HCV) infection. This observational single arm prospective study included 30 treatment-naive children (20 males) with proved chronic HCV fulfilling inclusion criteria. Their body weights ranged from 17 to 26 kg. All the included children received a single oral dose of LED/SOF 45/200 mg for 8 wk. Body weight, HCV-RNA, complete blood count, and liver function tests were monitored at 0, 2, 4, and 8 wk and sustained virol. response was evaluated after 12 wk after treatment (SVR12). The emergence of any side effects was also monitored. The most common risk factor (53.3%) was an parent or sibling with HCV infection. Twenty-nine patients (96.7%) were neg. for HCV-RNA by week 2 of treatment and 1 patient became neg. by week 4. The end of treatment response and SVR12 were 100%. Transaminases levels declined and returned to normal levels by week 2. Major side effects were fatigue in 90% (27/30) and headache in 76.7% (23/30). Side effects were minimal, tolerable, and did not interfere with daily activity or necessitate treatment discontinuation. A shortened 8-wk regimen of LED/SOF (45/200 mg) is safe and effective with 100% SVR12 in treatment-naive children with cirrhosis aged 4-10 years with chronic HCV infection genotype 4.

Journal of Pediatrics (New York, NY, United States) published new progress about Antiviral agents. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Computed Properties of 58-97-9.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Xue, Ying’s team published research in Molecules in 2019 | 58-97-9

Molecules published new progress about Nucleic acids Role: THU (Therapeutic Use), BIOL (Biological Study), USES (Uses). 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Electric Literature of 58-97-9.

Xue, Ying; Jin, Wei; Xu, Xian-Shun; Yong, Li; Hu, Bin; Xiong, Jing; Hu, Xue-Mei; Qing, Lin-Sen; Xie, Jing published the artcile< Quality evaluation of Tricholoma matsutake based on the nucleic acid compounds by UPLC-TOF/MS and UPLC-QqQ/MS>, Electric Literature of 58-97-9, the main research area is Tricholoma nucleic acid UPLC TOF MS Southwest China; Tricholoma matsutake; UPLC-QqQ/MS; UPLC-TOF/MS; nucleic acid compound; quality evaluation.

So far, there has been no quality evaluation of Tricholoma matsutake. Nucleic acid compounds are a kind of functional ingredient in T. matsutake that is beneficial to human health. In this study, a UPLC-TOF/MS method was first used to scan and identify the potential nucleic acid compounds in T. matsutake. Based on the calculation of the mol. formula and subsequent confirmation by authentic standards, 15 nucleic acid compounds were unambiguously identified: adenosine, cytidine, guanosine, inosine, thymidine, uridine, xanthosine dehydrate, 2′- deoxyadenosine, 2′-deoxycytidine, 2′-deoxyguanosine, 2′-deoxyuridine, adenosine 5′- monophosphate, CMP, GMP, and uridine 5′- monophosphate. Then, a UPLC-QqQ/MS method was developed for the subsequent quant. anal. After validating the limits of quantification, detection, precision, repeatability, and recovery through a calibration curve, the content of 15 nucleic acid compounds was determined by the proposed UPLC-QqQ/MS method in 80 T. matsutake samples collected from different regions in Sichuan province, Southwest China. After the statistical anal., we suggest that the total content of nucleic acid compounds in the qualified T. matsutake should be higher than 24.49 mg/100 g. The results indicated that the combined use of UPLC-TOF/MS and UPLC-QqQ/MS is efficient for fast identification and determination of nucleic acid compounds to comprehensively evaluate the quality of T. matsutake.

Molecules published new progress about Nucleic acids Role: THU (Therapeutic Use), BIOL (Biological Study), USES (Uses). 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Electric Literature of 58-97-9.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Yang, Songqiu’s team published research in Journal of Physical Chemistry B in 2020-05-07 | 58-97-9

Journal of Physical Chemistry B published new progress about Electron attachment. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Quality Control of 58-97-9.

Yang, Songqiu; Zhang, Yan; Zhao, Xi published the artcile< Change of Initial Yield of a Hydrated Electron with Uridine Monophosphate Concentration Is Related to the Excitation Photon Energy in Transient Absorption Spectroscopy>, Quality Control of 58-97-9, the main research area is hydrated electron uridine monophosphate excitation photon transient absorption.

The initial yield of a hydrated electron (eaq-) in a solution under laser pulse irradiation was investigated by pump-probe transient absorption spectroscopy. The initial quantum yield of eaq- varies with the concentration of uridine monophosphate (UMP). The variation of the concentration of eaq- is often used to study the prehydrated electron (epre-) and eaq- attachment to UMP. The results of 320 and 260 nm excitations were compared. It was found that with the increase of UMP concentration, the initial yield of eaq- increases at 320 nm excitation, but decreases at 260 nm excitation. The further anal. indicates that some of the epre- attachments to UMP before solvation at 260 nm excitation result in the decrease of the eaq- yield. In addition, the absorption of UMP to 260 nm also causes the decrease of the eaq- yield. After the excitation at 320 nm, the phosphate group of UMP can release electrons more easily than that of water mols. by two-photon absorption, and therefore the eaq- yield increases. With the increase of UMP concentration, the decay rate of eaq- increases because eaq- is captured by UMP. The change of excitation photon does not affect the reaction rate of eaq- attachment to UMP. The longer lifetime of eaq- obtained at 260 nm excitation than 320 nm excitation is induced by the larger eaq- escape probability at 260 nm excitation. Our results show that the femtosecond pulse pump-probe transient absorption spectroscopy method should be cautiously used because of its complexity in studying the epre- attachment to nucleotides in an aqueous solution

Journal of Physical Chemistry B published new progress about Electron attachment. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Quality Control of 58-97-9.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Niro, Giuliana’s team published research in Chemistry – A European Journal in 2020-12-21 | 58-97-9

Chemistry – A European Journal published new progress about Antibacterial agent resistance. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Name: ((2R,3S,4R,5R)-5-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl dihydrogen phosphate.

Niro, Giuliana; Weck, Stefanie C.; Ducho, Christian published the artcile< Merging Natural Products: Muraymycin-Sansanmycin Hybrid Structures as Novel Scaffolds for Potential Antibacterial Agents>, Name: ((2R,3S,4R,5R)-5-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl dihydrogen phosphate, the main research area is muraymycin sansanmycin hybrid structure scaffold antibacterial agent; antibiotics; hybrid structures; natural products; nucleosides; structure-activity relationship.

To overcome bacterial resistances, the need for novel antimicrobial agents is urgent. The class of so-called nucleoside antibiotics furnishes promising candidates for the development of new antibiotics, as these compounds block a clin. unexploited bacterial target: the integral membrane protein MraY, a key enzyme in cell wall (peptidoglycan) biosynthesis. Nucleoside antibiotics exhibit remarkable structural diversity besides their uridine-derived core motifs. Some sub-classes also show specific selectivities towards different Gram-pos. and Gram-neg. bacteria, which are poorly understood so far. Herein, the synthesis of a novel hybrid structure is reported, derived from the 5′-defunctionalized uridine core moiety of muraymycins and the peptide chain of sansanmycin B, as a new scaffold for the development of antimicrobial agents. The reported muraymycin-sansanmycin hybrid scaffold showed nanomolar activity against the bacterial target enzyme MraY, but displayed no significant antibacterial activity against S. aureus, E. coli, and P. aeruginosa.

Chemistry – A European Journal published new progress about Antibacterial agent resistance. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Name: ((2R,3S,4R,5R)-5-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl dihydrogen phosphate.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Fan, Yi’s team published research in Science of the Total Environment in 2022-04-15 | 58-97-9

Science of the Total Environment published new progress about Coagulation. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Recommanded Product: ((2R,3S,4R,5R)-5-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl dihydrogen phosphate.

Fan, Yi; Sun, Guangrong; Kaw, Han Yeong; Zhu, Lizhong; Wang, Wei published the artcile< Analytical characterization of nucleotides and their concentration variation in drinking water treatment process>, Recommanded Product: ((2R,3S,4R,5R)-5-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl dihydrogen phosphate, the main research area is nucleotide concentration variation solid phase extraction drinking water treatment; Disinfection byproducts (DBPs); Drinking water; Nucleotides; Precursors; Solid phase extraction (SPE); Ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Nucleotides, as the basic building blocks of nucleic acids, widely exist in aqueous environment. In this study, we developed a solid phase extraction-high performance liquid chromatog.-tandem mass spectrometry (SPE-UPLC-MS/MS) method for the anal. of 5′-adenosine monophosphate (AMP), 5′-uridine monophosphate (UMP), 5′-cytidine monophosphate (CMP) and 5′-guanosine monophosphate (GMP). The method achieved limits of detection (LODs) of 0.1-1.0 ng/L, and recoveries of 85-95% for the four tested nucleotides. The occurrence and concentrations of the four nucleotides in water from eight representative drinking water treatment and distribution systems in China were determined using this method. All four nucleotides were detectable in water treatment plant (WTP) influent and effluent, at concentrations of up to 30 ng/L and with occurrence frequency of around 90%. The concentrations of identified nucleotides increased 3-10 times after 10 km of water age in the water distribution system. Biol. filters and coagulation increased the concentrations of nucleotides, conversely, active carbon, ozonation, and ultrafiltration membrane removed nucleotides in water. The effects of active carbon and coagulation were further confirmed using laboratory-controlled experiment In addition, monochlorinated nucleotides were identified as the chlorination products of nucleotides.

Science of the Total Environment published new progress about Coagulation. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Recommanded Product: ((2R,3S,4R,5R)-5-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl dihydrogen phosphate.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Brandao, Tiago A S’s team published research in Biochemistry in 2020-06-02 | 58-97-9

Biochemistry published new progress about Conformational transition. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Synthetic Route of 58-97-9.

Brandao, Tiago A. S.; Richard, John P. published the artcile< Orotidine 5'-monophosphate decarboxylase: The operation of active site chains within and across protein subunits>, Synthetic Route of 58-97-9, the main research area is orotidine monophosphate decarboxylase Saccharomyces active site subunit substrate.

The D37 and T100′ side chains of orotidine 5′-monophosphate decarboxylase (OMPDC) interact with the C-3′ and C-2′ ribosyl hydroxyl groups, resp., of the bound substrate. We compare the intra-subunit interactions of D37 with the inter-subunit interactions of T100′ by determining the effects of the D37G, D37A, T100’G, and T100’A substitutions on the following: (a) kcat and kcat/Km values for the OMPDC-catalyzed decarboxylations of OMP and 5-fluoroorotidine 5′-monophosphate (FOMP) and (b) the stability of dimeric OMPDC relative to the monomer. The D37G and T100’A substitutions resulted in 2 kcal mol-1 increases in ΔG† for kcat/Km for the decarboxylation of OMP, while the D37A and T100’G substitutions resulted in larger 4 and 5 kcal mol-1 increases, resp., in ΔG†. The D37G and T100’A substitutions both resulted in smaller 2 kcal mol-1 decreases in ΔG† for the decarboxylation of FOMP compared to that of OMP. These results show that the D37G and T100’A substitutions affect the barrier to the chem. decarboxylation step while the D37A and T100’G substitutions also affect the barrier to a slow, ligand-driven enzyme conformational change. Substrate binding induces the movement of an α-helix (G’98-S’106) toward the substrate C-2′ ribosyl hydroxy bound at the main subunit. The T100’G substitution destabilizes the enzyme dimer by 3.5 kcal mol-1 compared to the monomer, which is consistent with the known destabilization of α-helixes by the internal Gly side chains [Serrano, L., et al. (1992) Nature, 356, 453-455]. We propose that the T100’G substitution weakens the α-helical contacts at the dimer interface, which results in a decrease in the dimer stability and an increase in the barrier to the ligand-driven conformational change.

Biochemistry published new progress about Conformational transition. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Synthetic Route of 58-97-9.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem