72,148 results match your criteria catalytic subunit

A new layer of phosphoinositide-mediated allosteric regulation uncovered for SHIP2.

FASEB J 2021 08;35(8):e21815

Structural and Chemical Biology, Centro de Investigaciones Biológicas Margarita Salas, Spanish National Research Council (CSIC), Madrid, Spain.

The Src homology 2 containing inositol 5-phosphatase 2 (SHIP2) is a large multidomain enzyme that catalyzes the dephosphorylation of the phospholipid phosphatidylinositol 3,4,5-triphosphate (PI(3,4,5)P ) to form PI(3,4)P . PI(3,4,5)P is a key lipid second messenger controlling the recruitment of signaling proteins to the plasma membrane, thereby regulating a plethora of cellular events, including proliferation, growth, apoptosis, and cytoskeletal rearrangements. SHIP2, alongside PI3K and PTEN, regulates PI(3,4,5)P levels at the plasma membrane and has been heavily implicated in serious diseases such as cancer and type 2 diabetes; however, many aspects of its regulation mechanism remain elusive. Read More

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The role of YTH domain containing 2 in epigenetic modification and immune infiltration of pan-cancer.

J Cell Mol Med 2021 Jul 27. Epub 2021 Jul 27.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

YTH domain containing 2 (YTHDC2) is the largest N6-Methyladenosine (m A) binding protein of the YTH protein family and the only member containing ATP-dependent RNA helicase activity. For further analysing its biological role in epigenetic modification, we comprehensively explored YTHDC2 from gene expression, genetic alteration, protein-protein interaction (PPI) network, immune infiltration, diagnostic value and prognostic value in pan-cancer, using a series of databases and bioinformatic tools. We found that YTHDC2 with Missense mutation could cause a different prognosis in uterine corpus endometrial carcinoma (UCEC), and its different methylation level could lead to a totally various prognosis in adrenocortical carcinoma (ACC), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), lung squamous cell carcinoma (LUSC) and UCEC. Read More

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Double MS2 guided restoration of genetic code in amber (TAG), opal (TGA) and ochre (TAA) stop codon.

Enzyme Microb Technol 2021 Sep 11;149:109851. Epub 2021 Jun 11.

Area of Bioscience and Biotechnology, School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomicity, Ishikawa, 923-1292, Japan. Electronic address:

The popularity and promise of gene therapy for common genetic diseases are currently increasing. Although effective treatments for genetic disorders are rare, editing of the mutated gene is a possible therapeutic approach for conditions caused by stop codon mutations, including either amber (TAG), opal (TGA) or ochre (TAA) stop codons. Restoration of point-mutated RNAs using artificial RNA editing can be used to modify gene-encoded information and generate functionally distinct proteins from a single gene. Read More

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September 2021

Autodisplay of an endo-1,4-β-xylanase from Clostridium cellulovorans in Escherichia coli for xylans degradation.

Enzyme Microb Technol 2021 Sep 27;149:109834. Epub 2021 May 27.

División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica (IPICYT), Camino a la Presa de San José 2055 Lomas 4ª. Sección, C.P. 78216, San Luis Potosí, Mexico. Electronic address:

The goal of this work was the autodisplay of the endo β-1,4-xylanase (XynA) from Clostridium cellulovorans in Escherichia coli using the AIDA system to carry out whole-cell biocatalysis and hydrolysate xylans. For this, pAIDA-xynA vector containing a synthetic xynA gene was fused to the signal peptide of the toxin subunit B Vibro cholere (ctxB) and the auto-transporter of the synthetic aida gene, which encodes for the connector peptide and β-barrel of the auto-transporter (AT-AIDA). E. Read More

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September 2021

Structure of the mini-RNA-guided endonuclease CRISPR-Cas12j3.

Nat Commun 2021 07 22;12(1):4476. Epub 2021 Jul 22.

Structural Molecular Biology Group, Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and Medical Sciences University of Copenhagen, Copenhagen, Denmark.

CRISPR-Cas12j is a recently identified family of miniaturized RNA-guided endonucleases from phages. These ribonucleoproteins provide a compact scaffold gathering all key activities of a genome editing tool. We provide the first structural insight into the Cas12j family by determining the cryoEM structure of Cas12j3/R-loop complex after DNA cleavage. Read More

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Novel Ag/cellulose-doped CeO quantum dots for efficient dye degradation and bactericidal activity with molecular docking study.

Carbohydr Polym 2021 Oct 17;269:118346. Epub 2021 Jun 17.

Department of Physics, Riphah Institute of Computing and Applied Sciences (RICAS), Riphah International University, 14 Ali Road, Lahore, Pakistan.

In the present study, the novel Ag/cellulose nanocrystal (CNC)-doped CeO quantum dots (QDs) with highly efficient catalytic performance were synthesized using one pot co-precipitation technique, which were then applied in the degradation of methylene blue and ciprofloxacin (MBCF) in wastewater. Catalytic activity against MBCF dye was significantly reduced (99.3%) for (4%) Ag dopant concentration in acidic medium. Read More

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October 2021

PRMT4 inhibitor TP-064 inhibits the pro-inflammatory macrophage lipopolysaccharide response in vitro and ex vivo and induces peritonitis-associated neutrophilia in vivo.

Biochim Biophys Acta Mol Basis Dis 2021 Jul 23:166212. Epub 2021 Jul 23.

Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333, CC, Leiden, The Netherlands.

Previous in vitro studies have shown that protein arginine N-methyltransferase 4 (PRMT4) is a co-activator for an array of cellular activities, including NF-κB -regulated pro-inflammatory responses. Here we investigated the effect of PRMT4 inhibitor TP-064 treatment on macrophage inflammation in vitro and in vivo. Exposure of RAW 264. Read More

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Insights into substrate recognition and specificity for IgG by Endoglycosidase S2.

PLoS Comput Biol 2021 Jul 26;17(7):e1009103. Epub 2021 Jul 26.

University of Maryland Computer-Aided Drug Design Center, Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland, United States of America.

Antibodies bind foreign antigens with high affinity and specificity leading to their neutralization and/or clearance by the immune system. The conserved N-glycan on IgG has significant impact on antibody effector function, with the endoglycosidases of Streptococcus pyogenes deglycosylating the IgG to evade the immune system, a process catalyzed by the endoglycosidase EndoS2. Studies have shown that two of the four domains of EndoS2, the carbohydrate binding module (CBM) and the glycoside hydrolase (GH) domain site are critical for catalytic activity. Read More

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A Single Point Mutation Controls the Rate of Interconversion Between the and Rotamers of the Histidine 189 χ2 Angle That Activates Bacterial Enzyme I for Catalysis.

Front Mol Biosci 2021 8;8:699203. Epub 2021 Jul 8.

Department of Chemistry, Iowa State University, Ames, IA, United States.

Enzyme I (EI) of the bacterial phosphotransferase system (PTS) is a master regulator of bacterial metabolism and a promising target for development of a new class of broad-spectrum antibiotics. The catalytic activity of EI is mediated by several intradomain, interdomain, and intersubunit conformational equilibria. Therefore, in addition to its relevance as a drug target, EI is also a good model for investigating the dynamics/function relationship in multidomain, oligomeric proteins. Read More

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EST-SSR-based landscape genetics of , a tertiary relict conifer endemic to China.

Ecol Evol 2021 Jul 15;11(14):9498-9515. Epub 2021 Jun 15.

Research Institute of Sun Yat-sen University in Shenzhen Shenzhen China.

, belonging to the monotypic genus (Taxaceae), is a relict conifer endemic to China. Its populations are usually small and patchily distributed, having a low capacity of natural regeneration. To gain a clearer understanding of how landscape variables affect the local adaptation of . Read More

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Salinomycin triggers prostate cancer cell apoptosis by inducing oxidative and endoplasmic reticulum stress via suppressing Nrf2 signaling.

Exp Ther Med 2021 Sep 1;22(3):946. Epub 2021 Jul 1.

The Fourth Department of Oncology, Yantai Hospital of Traditional Chinese Medicine, Yantai, Shandong 264001, P.R. China.

Salinomycin is a polyether antiprotozoal antibiotic that is widely used as an animal food additive. Some antifungal, antiparasitic, antiviral and anti-inflammatory activities have been reported for salinomycin. Recently, the anti-cancer effect of salinomycin has been demonstrated in breast cancer; however, the underlying mechanism remains unknown. Read More

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September 2021

High Expression of Citron Kinase Contributes to the Development of Esophageal Squamous Cell Carcinoma.

Front Genet 2021 7;12:628547. Epub 2021 Jul 7.

Department of Integrative Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Objective: This study aimed to investigate the role and potential regulatory mechanism of citron kinase (CIT) in esophageal squamous cell carcinoma (ESCC).

Methods: Citron kinase (CIT) expression in ESCC tissues was analyzed based on the microarray dataset GSE20347, and CIT expression in ESCC cell lines was analyzed. Eca-109 cells were lentivirally transfected with shRNA-CIT (LV-shCIT) to knock down CIT, followed by investigation of cell proliferation and apoptosis. Read More

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Phenylethanoid Glycosides From Callicarpa kwangtungensis Chun Attenuate TNF-α-Induced Cell Damage by Inhibiting NF-κB Pathway and Enhancing Nrf2 Pathway in A549 Cells.

Front Pharmacol 2021 7;12:693983. Epub 2021 Jul 7.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.

Acute lung injury (ALI) is a complicated and severe lung disease, which is often characterized by acute inflammation. Poliumoside (POL), acteoside (ACT) and forsythiaside B (FTB) are phenylethanoid glycosides (PGs) with strong antioxidant, anti-inflammatory, and anti-apoptotic properties, which are extracted from (CK). The aim of this study was to investigate the protective effects of POL, ACT, and FTB against TNF-α-induced damage using an ALI cell model and explore their potential mechanisms. Read More

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Computational investigation of FDA approved drugs as selective PARP-1 inhibitors by targeting BRCT domain for cancer therapy.

J Mol Graph Model 2021 Apr 6;108:107919. Epub 2021 Apr 6.

Postgraduate and Research Department of Botany, Arignar Anna Government Arts College, Villupuram, Tamil Nadu, India.

Poly(ADP-ribose) polymerase-1 is a promising target for the treatment of cancer due to its involvement in base excision repair pathways for repairing DNA single-strand breaks. However, available PARP-1 inhibitors target a highly conserved PARPs catalytic domain, which causes toxicity due to the off-target activity. Therefore, the present study was hypothesized to identify selective inhibitors by targeting specific protein-protein interacting (PPI) PARP-1 BRCT domain. Read More

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Selective Inhibition of the C-Domain of ACE (Angiotensin-Converting Enzyme) Combined With Inhibition of NEP (Neprilysin): A Potential New Therapy for Hypertension.

Hypertension 2021 Jul 26:HYPERTENSIONAHA12117041. Epub 2021 Jul 26.

Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (R.A.-L., A.C.M., K.B.N., A.H., F.J.R., D.S.S., T.J.G., D.G., R.M.T.).

Combined inhibition of NEP (neutral endopeptidase) and ACE (angiotensin-converting enzyme), without unwanted effects, remains an attractive therapeutic strategy in cardiovascular medicine. Omapatrilat, a dual NEP inhibitor-ACE inhibitor, was a promising antihypertensive drug but failed in trials due to angioedema, an effect possibly caused by inhibition of both the N- and C-domains of ACE. Here, we aimed to determine whether lisinopril-tryptophan (lisW-S), a C-domain specific ACE inhibitor that preserves the N-domain catalytic activity, together with sacubitril (NEP inhibitor), differentially influences cardiovascular function and vascular permeability in hypertension compared with omapatrilat and lisinopril+sacubitril which inhibits both the ACE C- and N-domains. Read More

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Phosphorylation-dependent subcellular redistribution of small myosin light chain kinase.

Biochim Biophys Acta Mol Cell Res 2021 Jul 22;1868(11):119104. Epub 2021 Jul 22.

National Medical Research Center for Cardiology, 3rd Cherepkovskaya St., 15a, Moscow 121552, Russian Federation.

Background: Myosin light chain kinase (MLCK) is a Ca-calmodulin-dependent enzyme dedicated to phosphorylate and activate myosin II to provide force for various motile processes. In smooth muscle cells and many other cells, small MLCK (S-MLCK) is a major isoform. S-MLCK is an actomyosin-binding protein firmly attached to contractile machinery in smooth muscle cells. Read More

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Updating Insights into the Catalytic Domain Properties of Plant () and () Proteins.

Molecules 2021 Jul 17;26(14). Epub 2021 Jul 17.

Department of Biotechnology, Agricultural University of Athens, 11855 Athens, Greece.

The wall is the last frontier of a plant cell involved in modulating growth, development and defense against biotic stresses. Cellulose and additional polysaccharides of plant cell walls are the most abundant biopolymers on earth, having increased in economic value and thereby attracted significant interest in biotechnology. Cellulose biosynthesis constitutes a highly complicated process relying on the formation of cellulose synthase complexes. Read More

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Synthesis and In Vitro Evaluation of C-7 and C-8 Luteolin Derivatives as Influenza Endonuclease Inhibitors.

Int J Mol Sci 2021 Jul 20;22(14). Epub 2021 Jul 20.

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences and IOCB Research Center, Flemingovo n. 2, 166 10 Prague, Czech Republic.

The part of the influenza polymerase PA subunit featuring endonuclease activity is a target for anti-influenza therapies, including the FDA-approved drug Xofluza. A general feature of endonuclease inhibitors is their ability to chelate Mg or Mn ions located in the enzyme's catalytic site. Previously, we screened a panel of flavonoids for PA inhibition and found luteolin and its C-glucoside orientin to be potent inhibitors. Read More

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mA RNA methylation regulates promoter- proximal pausing of RNA polymerase II.

Mol Cell 2021 Jul 20. Epub 2021 Jul 20.

Université Clermont Auvergne, CNRS UMR6293, Inserm U1103, GReD institute, 63000 Clermont-Ferrand, France. Electronic address:

RNA polymerase II (RNAP II) pausing is essential to precisely control gene expression and is critical for development of metazoans. Here, we show that the mA RNA modification regulates promoter-proximal RNAP II pausing in Drosophila cells. The mA methyltransferase complex (MTC) and the nuclear reader Ythdc1 are recruited to gene promoters. Read More

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Editing Domain Motions Preorganize the Synthetic Active Site of Prolyl-tRNA Synthetase.

ACS Catal 2020 Sep 14;10(17):10229-10242. Epub 2020 Aug 14.

Department of Chemistry and Biochemistry, University of Wisconsin-Eau Claire, WI, 54701, USA.

Prolyl-tRNA synthetases (ProRSs) catalyze the covalent attachment of proline onto cognate tRNAs, an indispensable step for protein synthesis in all living organisms. ProRSs are modular enzymes and the "prokaryotic-like" ProRSs are distinguished from "eukaryotic-like" ProRSs by the presence of an editing domain (INS) inserted between motifs 2 and 3 of the main catalytic domain. Earlier studies suggested the presence of coupled-domain dynamics could contribute to catalysis; however, the role that the distal, highly mobile INS domain plays in catalysis at the synthetic active site is not completely understood. Read More

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September 2020

Endocytosis of the CdtA subunit from the Haemophilus ducreyi cytolethal distending toxin.

Cell Microbiol 2021 Jul 22:e13380. Epub 2021 Jul 22.

Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL.

Many Gram-negative pathogens produce a cytolethal distending toxin (CDT) with two cell-binding subunits (CdtA + CdtC) and a catalytic CdtB subunit. After adhesion to the plasma membrane of a target cell, CDT moves by retrograde transport to endoplasmic reticulum. CdtB then enters the nucleus where it generates DNA breaks that lead to cell cycle arrest and apoptosis or senescence. Read More

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Structural basis of human separase regulation by securin and CDK1-cyclin B1.

Nature 2021 Jul 21. Epub 2021 Jul 21.

Department of Molecular Biology, University of Geneva, Geneva, Switzerland.

In early mitosis, the duplicated chromosomes are held together by the ring-shaped cohesin complex. Separation of chromosomes during anaphase is triggered by separase-a large cysteine endopeptidase that cleaves the cohesin subunit SCC1 (also known as RAD21). Separase is activated by degradation of its inhibitors, securin and cyclin B, but the molecular mechanisms of separase regulation are not clear. Read More

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A new immunochemical strategy for triple-negative breast cancer therapy.

Sci Rep 2021 Jul 21;11(1):14875. Epub 2021 Jul 21.

Department of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA.

Triple-negative breast cancer (TNBC) is a highly diverse group of malignant neoplasms which tend to have poor outcomes, and the development of new targets and strategies to treat these cancers is sorely needed. Antibody-drug conjugate (ADC) therapy has been shown to be a promising targeted therapy for treating many cancers, but has only rarely been tried in patients with TNBC. A major reason the efficacy of ADC therapy in the setting of TNBC has not been more fully investigated is the lack of appropriate target molecules. Read More

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Cryo-EM structure of the human ELMO1-DOCK5-Rac1 complex.

Sci Adv 2021 Jul 21;7(30). Epub 2021 Jul 21.

RIKEN Center for Biosystems Dynamics Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.

The dedicator of cytokinesis (DOCK) family of guanine nucleotide exchange factors (GEFs) promotes cell motility, phagocytosis, and cancer metastasis through activation of Rho guanosine triphosphatases. Engulfment and cell motility (ELMO) proteins are binding partners of DOCK and regulate Rac activation. Here, we report the cryo-electron microscopy structure of the active ELMO1-DOCK5 complex bound to Rac1 at 3. Read More

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Detection of Catalytically Linked Conformational Changes in Wild-Type Class Ia Ribonucleotide Reductase Using Reaction-Induced FTIR Spectroscopy.

J Phys Chem B 2021 Jul 21. Epub 2021 Jul 21.

Department of Chemistry and Biochemistry and the Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, United States.

The enzyme, ribonucleotide reductase (RNR), is essential for DNA synthesis in all cells. The class Ia RNR consists of two dimeric subunits, α and β, which form an active but unstable heterodimer of dimers, αβ. The structure of the wild-type form of the enzyme has been challenging to study due to the instability of the catalytic complex. Read More

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Structural Aspects of mTOR Inhibitors: In Progress to Search Potential Compounds.

Anticancer Agents Med Chem 2021 Jul 20. Epub 2021 Jul 20.

Department of Pharmaceutical Chemistry, ISF College of Pharmacy, GT Road, Ghal Kalan, Moga-142001, Punjab, India.

mTOR (mammalian target of rapamycin) is a catalytic subunit composed of two multi-protein complexes that indicate mTORC1, mTORC2. It plays a crucial role in various fundamental cell processes like cell proliferation, metabolism, survival, cell growth, etc. Various first line mTOR inhibitors such as Rapamycin, Temsirolimus, Everolimus, Ridaforolimus, Umirolimus, Zotarolimus have been used popularly. Read More

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Redox Isomerism in the S3 State of the Oxygen-Evolving Complex Resolved by Coupled Cluster Theory.

Chemistry 2021 Jul 19. Epub 2021 Jul 19.

Max-Planck-Institut für Kohlenforschung, Molecular Theory and Spectroscopy, Kaiser-Wilhelm-Platz 1, 45470, Muelheim an der Ruhr, GERMANY.

The electronic and geometric structures of the water oxidizing complex of Photosystem II in the steps of the catalytic cycle that precede dioxygen evolution remain hotly debated. Recent structural and spectroscopic investigations support contradictory redox formulations for the active-site Mn4CaO x cofactor in the final metastable S3 state. These range from the widely accepted Mn(IV)4 oxo-hydroxo model, which presumes O-O bond formation to occur in the ultimate transient intermediate (S4) of the catalytic cycle, to a Mn(III)2Mn(IV)2 peroxo model representative of the contrasting "early-onset" O-O bond formation hypothesis. Read More

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Evaluation of model refinement in CASP14.

Proteins 2021 Jul 20. Epub 2021 Jul 20.

Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.

We report here an assessment of the model refinement category of the 14th round of Critical Assessment of Structure Prediction (CASP14). As before, predictors submitted up to five ranked refinements, along with associated residue-level error estimates, for targets that had a wide range of starting quality. The ability of groups to accurately rank their submissions and to predict coordinate error varied widely. Read More

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Germline and Somatic mutations in postmenopausal breast cancer patients.

Clinics (Sao Paulo) 2021 16;76:e2837. Epub 2021 Jul 16.

Departamento de Radiologia e Oncologia, Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR.

Objectives: In breast cancer (BC) patients, the frequency of germline BRCA mutations (gBRCA) may vary according to the ethnic background, age, and family history of cancer. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the second most common somatic mutated gene in BC; however, the association of mutations in both genes with cancer has not been thoroughly investigated. Thus, our aims were to investigate gBRCA mutation frequency in a cohort of postmenopausal Brazilian BC patients and the association of gBRCA1/BRCA2 and PIK3CA somatic mutations. Read More

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Molecular insights into the endoperoxide formation by Fe(II)/α-KG-dependent oxygenase NvfI.

Nat Commun 2021 07 20;12(1):4417. Epub 2021 Jul 20.

Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Endoperoxide-containing natural products are a group of compounds with structurally unique cyclized peroxide moieties. Although numerous endoperoxide-containing compounds have been isolated, the biosynthesis of the endoperoxides remains unclear. NvfI from Aspergillus novofumigatus IBT 16806 is an endoperoxidase that catalyzes the formation of fumigatonoid A in the biosynthesis of novofumigatonin. Read More

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